研究者詳細 - 前田　恵

論文 - 前田　恵

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Construction of tomato plants with suppressed endo-β-N-acetylglucosaminidase activity using CRISPR-Cas9 mediated genome editing. 査読国際誌

Naoko Okamoto, Megumi Maeda, Chiharu Yamamoto, Reo Kodama, Koichi Sugimoto, Yoshihito Shinozaki, Hiroshi Ezura, Yoshinobu Kimura

Plant physiology and biochemistry : PPB 190 203 - 211 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

High mannose-type free N-glycans with a single N-acetyl-D-glucosamine (GlcNAc) residue at the reducing end (GN1-HMT-FNGs) are produced by cytosolic endo-β-N-acetylglucosaminidase (EC:3.2.1.96) (ENGase) and are ubiquitous in differentiating and growing plant cells. To elucidate the physiological functions of HMT-FNGs in plants, we identified the ENGase gene in tomato (Solyc06g050930) and detected ENGase activity and increased production of GN1-HMT-FNGs during tomato fruit maturation. However, the precise role of GN1-HMT-FNGs in fruit maturation remains unclear. In this study, we established tomato ENGase mutants with suppressed ENGase activity via CRISPR/Cas9 genome editing technology. DNA sequencing of the Δeng mutants (T0 and T1 generations) revealed that they had the same mutations in the genomic DNA around the target sequences. Three null CRISPR/Cas9 segregant plants of the T1 generation (Δeng1-2, -22, and -26) were used to measure ENGase activity and analyze the structural features of HMT-FNGs in the leaves. The Δeng mutants did not exhibit ENGase activity and produced GN2-HMT-FNGs bearing tow GlcNAc residues at the reducing end side instead of GN1-HMT-FNGs. The Δeng mutants lack the N-terminal region of ENGase, indicating that the N-terminal region is important for full ENGase activity. The fruits of Δeng mutants (T2 generation) also showed loss of ENGase activity and similar structural features of HMT-FNGs of the T1 generation. However, there was no significant difference in fruit maturation between the T2 generation of the Δeng mutants and the wild type. The Δeng mutants rich in GN2-HMT-FNGs could be offered as a new tomato that is different from wild type containing GN1-HMT-FNGs.

DOI： 10.1016/j.plaphy.2022.08.009

Structural features of free N-glycans in α1,3/4-fucosidase-deficient Arabidopsis thaliana: deletion of α1,3/4-fucosidase activity induced accumulation of plant complex type GN1 free N-glycans. 査読国際誌

Shun Takata, Megumi Hayashi, Megumi Maeda, Takeshi Ishimizu, Yoshinobu Kimura

Bioscience, biotechnology, and biochemistry 86 ( 10 ) 1413 - 1416 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Deletion of α-1,3/4-fucosidase activity in Arabidopsis thaliana resulted in the accumulation of GN1-type free N-glycans with the Lewis a epitope (GN1-FNG). This suggests that the release of α-fucose residue(s) may trigger rapid degradation of the plant complex-type (PCT) GN1-FNG. The fact that PCT-GN1-FNG has rarely been detected to date is probably due to its easier degradation compared with PCT-GN2-FNG.

DOI： 10.1093/bbb/zbac120

Improved method for preparation and purification of recombinant α-synuclein: high-mannose-type free N-glycan prepared from an edible bean (Vigna angulari, Azuki bean) inhibits α-synuclein aggregation. 査読国際誌

Shota Kosaka, Makoto Katsube, Megumi Maeda, Yoshinobu Kimura

Bioscience, biotechnology, and biochemistry 86 ( 6 ) 770 - 774 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Parkinson's disease is characterized by the accumulation of amyloid, which consists of α-synuclein (α-Syn). To screen compounds with amyloid aggregation inhibitory activity, an effective method for the preparation of α-Syn is a prerequisite. We established a simpler method for α-Syn preparation using freeze-thaw treatment of transformed Escherichia coli. Furthermore, we found that the high-mannose type free N-glycans could prevent α-Syn aggregation.

DOI： 10.1093/bbb/zbac040

Improved assay system for acidic peptide: N-glycanase (aPNGase) activity in plant extracts. 査読国際誌

Chiharu Yamamoto, Mikako Ogura, Ryota Uemura, Maeda Megumi, Hiroyuki Kajiura, Ryo Misaki, Kazuhito Fujiyama, Yoshinobu Kimura

Analytical biochemistry 634 114367 - 114367 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Plant acidic peptide: N-glycanase (aPNGase) release N-glycans from glycopeptides during the degradation process of glycoproteins in developing or growing plants. We have previously developed a new method to detect the aPNGase activity in crude extracts, which is prerequisite for the construction of aPNGase knockout or overexpression lines. However, this method has the disadvantage of requiring de-sialylation treatment and a lectin chromatography. In this study, therefore, we improved the simple and accurate method for detecting aPNGase activity using anion-exchange HPLC requiring neither the desialylation treatment nor the lectin affinity chromatography.

DOI： 10.1016/j.ab.2021.114367

Large-scale preparation of sialyl-Tn antigen-containing peptides from mucin-like glycoproteins in boar seminal gel. 査読国際誌

Ryota Takeuchi, Megumi Maeda, Miran Nakano, Hiroaki Funahashi, Yoshinobu Kimura

Bioscience, biotechnology, and biochemistry 85 ( 9 ) 2022 - 2025 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sialyl-Tn antigen, a tumor antigen, is a valuable ligand for the purification of proteins that specifically bind to it. Here, we developed a new method for the preparation of large amounts of sialyl-Tn antigen-containing peptides from an unused resource, boar seminal gel. The glycopeptides were prepared from the actinase E digests by a combination of gel filtration and hydrophilic partitioning.

DOI： 10.1093/bbb/zbab114

Purification, Characterization, and Gene Expression of Rice Endo-β-N-Acetylglucosaminidase, Endo-Os 査読国際誌

Megumi Maeda, Naoko Okamoto, Norie Araki, Yoshinobu Kimura

Frontiers in Plant Science 12 647684 - 647684 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

In the endoplasmic reticulum-associated degradation system of plant and animal cells, high-mannose type free <italic>N</italic>-glycans (HMT-FNGs) are produced from misfolded glycoproteins prior to proteasomal degradation, and two enzymes, cytosolic peptide:<italic>N</italic>-glycanase (cPNGase) and endo-β-<italic>N-</italic>acetylglucosaminidase (endo-β-GlcNAc-ase), are involved in the deglycosylation. Although the physiological functions of these FNGs in plant growth and development remain to be elucidated, detailed characterization of cPNGase and endo-β-GlcNAc-ase is required. In our previous work, we described the purification, characterization, and subcellular distribution of some plant endo-β-GlcNAc-ases and preliminarily reported the gene information of rice endo-β-GlcNAc-ase (Endo-Os). Furthermore, we analyzed the changes in gene expression of endo-β-GlcNAc-ase during tomato fruit maturation and constructed a mutant line of <italic>Arabidopsis thaliana</italic>, in which the two endo-β-GlcNAc-ase genes were knocked-out based on the Endo-Os gene. In this report, we describe the purification, characterization, amino acid sequence, and gene cloning of Endo-Os in detail. Purified Endo-Os, with an optimal pH of 6.5, showed high activity for high-mannose type <italic>N</italic>-glycans bearing the Manα1-2Manα1-3Manβ1 unit; this substrate specificity was almost the same as that of other plant endo-β-GlcNAc-ases, suggesting that Endo-Os plays a critical role in the production of HTM-FNGs in the cytosol. Electrospray ionization-mass spectrometry analysis of the tryptic peptides revealed 17 internal amino acid sequences, including the C terminus; the N-terminal sequence could not be identified due to chemical modification. These internal amino acid sequences were consistent with the amino acid sequence (UniProt ID: Q5W6R1) deduced from the <italic>Oryza sativa</italic> cDNA clone AK112067 (gene ID: <italic>Os05g0346500</italic>). Recombinant Endo-Os expressed in <italic>Escherichia coli</italic> using cDNA showed the same enzymatic properties as those of native Endo-Os.

DOI： 10.3389/fpls.2021.647684

Direct evidence of cytosolic PNGase activity in Arabidopsis thaliana: in vitro assay system for plant cPNGase activity 査読国際誌

Sahoko Shirai, Ryota Uemura, Megumi Maeda, Hiroyuki Kajiura, Ryo Misaki, Kazuhito Fujiyama, Yoshinobu Kimura

Bioscience, Biotechnology, and Biochemistry 85 ( 6 ) 1460 - 1463 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

<title>ABSTRACT</title>
Cytosolic peptide:N-glycanase (cPNGase), which occurs ubiquitously in eukaryotic cells, is involved in the de-N-glycosylation of misfolded glycoproteins in the protein quality control system. In this study, we aimed to provide direct evidence of plant cPNGase activity against a denatured glycoprotein using a crude extract prepared from a mutant line of Arabidopsis thaliana lacking 2 acidic PNGase genes.

DOI： 10.1093/bbb/zbab047

その他リンク： http://academic.oup.com/bbb/article-pdf/85/6/1460/38192129/zbab047.pdf

Purification and molecular characterization of a truncated-type Ara h 1, a major peanut allergen: oligomer structure, antigenicity, and glycoform. 査読国際誌

Asaduzzaman Md, Megumi Maeda, Teruaki Matsui, Yoshihiro Takasato, Komei Ito, Yoshinobu Kimura

Glycoconjugate journal 38 ( 1 ) 67 - 76 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Peanut allergies are among the most severe food allergies, and several allergenic proteins referred to as Ara h 1-Ara h 17 have been identified from peanut seeds. The molecular characterization of Ara h 1 (63 kDa), a glycosylated allergen, has almost been completed, and the occurrence of two homologous genes (clone 41B and clone P17) has been identified. In this study, we found a new variant of Ara h 1 i.e. 54 kDa, in which the N-terminal amino acid sequence was EGREGEQ-, indicating that the N-terminal domain of 63 kDa Ara h 1 had been removed. This new isoform was obtained from the run-through fraction of hydrophobic interaction chromatography while 63 kDa Ara h 1 was tightly bound to the hydrophobic resins, suggesting that the removal of the N-terminal domain resulted in extreme hydrophilic properties. We found that 63 kDa Ara h 1 occurs as higher order homo-oligomeric conformations such as decamer or nonamer, while 54 kDa Ara h 1 occurs exclusively as a homotrimer, indicating that the N-terminal domain of the 63 kDa molecule may be involved in higher order oligomerization. When antisera from peanut-allergic patients were treated with both the Ara h 1 molecules, the immunoglobulin E (IgE) antibodies in these sera reacted with each Ara h 1 molecule, suggesting that the C-terminal as well as the N-terminal domains of Ara h 1 contribute significantly to the epitope formations of this peanut glycoallergen. Furthermore, the glycoform analyses of N-glycans linked to 63 kDa and 54 kDa Ara h 1 subunits revealed that both typical high-mannose type and β-xylosylated type N-glycans are linked to the molecules. The cross-reactivity of IgE against Ara h 1 in the serum of one peanut allergy patient was completely lost by de-N-glycosylation, indicating the N-glycan of Ara h 1 was the sole epitope for the Ara h 1- specific IgE in the patient.

DOI： 10.1007/s10719-020-09969-1

Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes. 査読国際誌

Naoko Kumagai-Takei, Yasumitsu Nishimura, Megumi Maeda, Hiroaki Hayashi, Hidenori Matsuzaki, Suni Lee, Kei Yoshitome, Tatsuo Ito, Takemi Otsuki

Environmental health and preventive medicine 25 ( 1 ) 59 - 59 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8+ T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8+ T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8+ lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8+ lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8+ T cells, cultured human CD8+ T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8+ lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.

DOI： 10.1186/s12199-020-00900-6

Convenient preparation of an antigenic oligosaccharide from white kidney bean powder: A useful plant oligosaccharide for synthesis of immunoactive glycopolymer. 査読国際誌

Mariko Kimura, Mikako Ogura, Miyuki Akamatsu, Kaede Sugimoto, Megumi Maeda, Teruhiko Nitoda, Haruko Nagasawa-Fujimori, Hirotaka Yamashita, Yoshinobu Kimura

International journal of biological macromolecules 153 1016 - 1023 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Plant glycoproteins, especially allergenic glycoproteins such as pollen allergens, often carry antigenic N-glycans with α1-3 fucose and/or β1-2 xylose residue(s) on the trimannosyl core structure. We previously reported that one of such antigenic free-form N-glycans, Man3Xyl1Fuc1GlcNAc2 (M3FX) suppressed IL-4 production from Th2 cells of pollinosis patients. For the molecular-level analysis of this immunoactivity, an effective and convenient procedure for large scale preparation of the immunoactive free-form N-glycan and a synthesis of glycopolymers bearing multivalent M3FX has been required. During the preparation of prebiotic oligosaccharides from several edible beans, we found that the free-form M3FX accumulates in relatively large amounts in white kidney beans. In this report, we describe a new procedure for preparation of M3FX from white kidney bean powders by a combination of ion-exchange method, gel-filtration, and hydrophilic partitioning. The high-purity of M3FX prepared by this procedure was confirmed by MS-analysis and 1H-NMR, suggesting that the free-form M3FX can be used for the synthesis of neoglycopolymer. Using this new procedure, the immunoactive oligosaccharide can be prepared without the chemical method such as hydrazinolysis and other purification steps required to exclude other type of N-glycans.

DOI： 10.1016/j.ijbiomac.2019.10.231

Synthesis and preliminary evaluation of neoglycopolymers carrying multivalent N-glycopeptide units. 査読国際誌

Naoto Takeda, Megumi Maeda, Satsuki Itano, Miho Takase, Mariko Kimura, Yoshinobu Kimura

International journal of biological macromolecules 147 1294 - 1300 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

In the present study, for the discovery of uncharacterized glycan-binding receptors or lectin-like receptors in plants, we developed neoglycopolymers to which three types of N-glycopeptides are conjugated; the first with plant complex type N-glycan (M3FX), the second with high-mannose type N-glycan (M8), and the third with animal complex type N-glycan (NeuAc2Gal2GN2M3). Three types of Asn-oligosaccharide (Asn-M3FX, Asn-M8, or Asn-NeuAc2Gal2GN2M3) were prepared from storage glycoproteins of Ginkgo biloba seeds, Vigna angularis seeds, and egg yolk glycopeptides from actinase digests of each glycoproteins or glycopeptide. Neoglycopolymers were synthesized such that the α-amino groups of Asn-oligosaccharide were coupled to the carboxyl groups of poly-γ-L-glutamic acid (γ-L-PGA) with 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate (DMT-MM). The resulting neoglycopolymers were purified through a combination of gel-filtration and reverse-phase HPLC. The incorporation of N-glycans into γ-L-PGA (mol%) was estimated through amino acid composition analysis after acid hydrolysis. The incorporation rates of Asn-M3FX, Asn-M8, and Asn-NeuAc2Gal2GN2M3 into γ-L-PGA were 15.4%, 8.6%, and 11.1%, indicating that nearly 890, 500, and 640 molecules of N-glycans were conjugated with γ-L-PGA, respectively. Furthermore, we confirmed that the neoglycopolymer carrying the multivalent high-mannose type N-glycans is a useful tool for rapid purification of mannose-binding protein, Concanavalin A, from jack bean extract.

DOI： 10.1016/j.ijbiomac.2019.09.255

Cytosolic Free N-Glycans Are Retro-Transported Into the Endoplasmic Reticulum in Plant Cells. 査読国際誌

Makoto Katsube, Natsuki Ebara, Megumi Maeda, Yoshinobu Kimura

Frontiers in plant science 11 610124 - 610124 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

During endoplasmic reticulum (ER)-associated degradation, free N-glycans (FNGs) are produced from misfolded nascent glycoproteins via the combination of the cytosolic peptide N-glycanase (cPNGase) and endo-β-N-acetylglucosaminidase (ENGase) in the plant cytosol. The resulting high-mannose type (HMT)-FNGs, which carry one GlcNAc residue at the reducing end (GN1-FNGs), are ubiquitously found in developing plant cells. In a previous study, we found that HMT-FNGs assisted in protein folding and inhibited β-amyloid fibril formation, suggesting a possible biofunction of FNGs involved in the protein folding system. However, whether these HMT-FNGs occur in the ER, an organelle involved in protein folding, remained unclear. On the contrary, we also reported the presence of plant complex type (PCT)-GN1-FNGs, which carry the Lewisa epitope at the non-reducing end, indicating that these FNGs had been fully processed in the Golgi apparatus. Since plant ENGase was active toward HMT-N-glycans but not PCT-N-glycans that carry β1-2xylosyl and/or α1-3 fucosyl residue(s), these PCT-GN1-FNGs did not appear to be produced from fully processed glycoproteins that harbored PCT-N-glycans via ENGase activity. Interestingly, PCT-GN1-FNGs were found in the extracellular space, suggesting that HMT-GN1-FNGs formed in the cytosol might be transported back to the ER and processed in the Golgi apparatus through the protein secretion pathway. As the first step in elucidating the production mechanism of PCT-GN1-FNGs, we analyzed the structures of free oligosaccharides in plant microsomes and proved that HMT-FNGs (Man9-7GlcNAc1 and Man9-8GlcNAc2) could be found in microsomes, which almost consist of the ER compartments.

DOI： 10.3389/fpls.2020.610124

Plant complex type free N-glycans occur in tomato xylem sap. 査読国際誌

Yuta Tsujimori, Mikako Ogura, Md Ziaur Rahman, Megumi Maeda, Yoshinobu Kimura

Bioscience, biotechnology, and biochemistry 83 ( 7 ) 1310 - 1314 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Free N-glycans (FNGs) are ubiquitous in growing plants. Further, acidic peptide:N-glycanase is believed to be involved in the production of plant complex-type FNGs (PCT-FNGs) during the degradation of dysfunctional glycoproteins. However, the distribution of PCT-FNGs in growing plants has not been analyzed. Here, we report the occurrence of PCT-FNGs in the xylem sap of the stem of the tomato plant. Abbreviations: RP-HPLC: reversed-phase HPLC; SF-HPLC: size-fractionation HPLC; PA-: pyridylamino; PCT: plant complex type; Hex: hexose; HexNAc: N-acetylhexosamine; Pen: pentose; Deoxyhex: deoxyhexose; Man: D-mannose; GlcNAc: N-acetyl-D-glucosamine; Xyl: D-xylose; Fuc: L-fucose; Lea: Lewis a (Galβ1-3(Fucα1-4)GlcNAc); PCT: plant complex type; M3FX: Manα1-6(Manα1-3)(Xylβ1-2)Manβ1-4GlcNAcβ1-4(Fucα1-3)GlcNAc-PA; GN2M3FX: GlcNAcβ1-2Manα1-6(GlcNAcβ1-2Manα1-3)(Xylβ1-2)Manβ1-4GlcNAcβ1-4(Fucα1-3)GlcNAc-PA; (Lea)1GN1M3FX: Galβ1-3(Fucα1-4)GlcNAc1-2 Manα1-6(GlcNAcβ1-2Manα1-3)(Xylβ1-2)Manβ1-4GlcNAcβ1-4(Fucα1-3)GlcNAc-PA or GlcNAc1-2Manα1-6(Galβ1-3(Fucα1-4)GlcNAc1-2Manα1-3)(Xylβ1-2)Manβ1-4GlcNAcβ1-4(Fucα1-3)GlcNAc-PA.

DOI： 10.1080/09168451.2019.1608803

アスベスト曝露によるヒト末梢血CD4+細胞からのIL-17産生誘導

大槻剛巳, 前田恵, 李順姫, 吉留敬, 武井直子, 西村泰光

産業衛生学雑誌 61 ( 臨増 ) 444 - 444 2019年5月

Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers. 査読国際誌

Maeda M, Matsuzaki H, Yamamoto S, Lee S, Kumagai-Takei N, Yoshitome K, Min Y, Sada N, Nishimura Y, Otsuki T

Oncology reports 40 ( 2 ) 748 - 758 2018年8月

Molecular characterization of second tomato α1,3/4-fucosidase (α-Fuc'ase Sl-2), a member of glycosyl hydrolase family 29 active toward the core α1,3-fucosyl residue in plant N-glycans. 査読国際誌

Md Ziaur Rahman, Yuta Tsujimori, Megumi Maeda, Md Anowar Hossain, Takeshi Ishimizu, Yoshinobu Kimura

Journal of biochemistry 164 ( 1 ) 53 - 63 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

In a previous study, we molecular-characterized a tomato (Solanum lycopersicum) α1, 3/4-fucosidase (α-Fuc'ase Sl-1) encoded in a tomato gene (Solyc03g006980), indicating that α-Fuc'ase Sl-1 is involved in the turnover of Lea epitope-containing N-glycans. In this study, we have characterized another tomato gene (Solyc11g069010) encoding α1, 3/4-fucosidase (α-Fuc'ase Sl-2), which is also active toward the complex type N-glycans containing Lea epitope(s). The baculovirus-insect cell expression system was used to express that α-Fuc'ase Sl-2 with anti-FLAG tag, and the expression product (rFuc'ase Sl-2), was found as a 65 kDa protein using SDS-PAGE and has an optimum pH of around 5.0. Similarly to rFuc'ase Sl-1, rFuc'ase Sl-2 hydrolyzed the non-reducing terminal α1, 3-fucose residue on LNFP III and α1, 4-fucose residues of Lea epitopes on plant complex type N-glycans, but not the core α1, 3-fucose residue on Manβ1-4GlcNAcβ1-4(Fucα1-3)GlcNAc or Fucα1-3GlcNAc. However, we found that both α-Fuc'ases Sl-1 and Sl-2 were specifically active toward α1, 3-fucose residue on GlcNAcβ1-4(Fucα1-3)GlcNAc, indicating that the non-substituted β-GlcNAc linked to the proximal GlcNAc residue of the core tri-saccharide moiety of plant specific N-glycans must be a pre-requisite for α-Fuc'ase activity. A 3 D modelled structure of the catalytic sites of α-Fuc'ase Sl-2 suggested that Asp192 and Glu236 may be important for binding to the α1, 3/4 fucose residue.

DOI： 10.1093/jb/mvy029

Novel assay system for acidic Peptide:N-glycanase (aPNGase) activity in crude plant extract. 査読国際誌

Ryota Uemura, Mikako Ogura, Chihiro Matsumaru, Tsuyoshi Akiyama, Megumi Maeda, Yoshinobu Kimura

Bioscience, biotechnology, and biochemistry 82 ( 7 ) 1172 - 1175 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Acidic peptide:N-glycanase (aPNGase) plays a pivotal role in plant glycoprotein turnover. For the construction of aPNGase-knockout or -overexpressing plants, a new method to detect the activity in crude plant extracts is required because endogenous peptidases present in the extract hamper enzyme assays using fluorescence-labeled N-glycopeptides as a substrate. In this study, we developed a new method for measuring aPNGase activity in crude extracts from plant materials.

DOI： 10.1080/09168451.2018.1459464

Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos. 査読国際誌

Kumagai-Takei N, Yamamoto S, Lee S, Maeda M, Masuzzaki H, Sada N, Yu M, Yoshitome K, Nishimura Y, Otsuki T

International journal of molecular sciences 19 ( 2 ) 2018年2月

Degradation pathway of plant complex-type n-glycans: Identification and characterization of a key α1,3-fucosidase from glycoside hydrolase family 29 査読国際誌

Shun Kato, Megumi Hayashi, Mai Kitagawa, Hiroyuki Kajiura, Megumi Maeda, Yoshinobu Kimura, Kiyohiko Igarashi, Masahiro Kasahara, Takeshi Ishimizu

Biochemical Journal 475 ( 1 ) 305 - 317 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Portland Press Ltd

Plant complex-type N-glycans are characterized by the presence of α1,3-linked fucose towards the proximal N-acetylglucosamine residue and β1,2-linked xylose towards the β-mannose residue. These glycans are ultimately degraded by the activity of several glycoside hydrolases. However, the degradation pathway of plant complex-type N-glycans has not been entirely elucidated because the gene encoding α1,3-fucosidase, a glycoside hydrolase acting on plant complex-type N-glycans, has not yet been identified, and its substrate specificity remains to be determined. In the present study, we found that AtFUC1 (an Arabidopsis GH29 α-fucosidase) is an α1,3-fucosidase acting on plant complex-type N-glycans. This fucosidase has been known to act on α1,4-fucoside linkage in the Lewis A epitope of plant complex-type N-glycans. We found that this glycoside hydrolase specifically acted on GlcNAcβ1–4(Fucα1–3)GlcNAc, a degradation product of plant complex-type N-glycans, by sequential actions of vacuolar α-mannosi-dase, β1,2-xylosidase, and endo-β-mannosidase. The AtFUC1-deficient mutant showed no distinct phenotypic plant growth features
however, it accumulated GlcNAcβ1–4 (Fucα1–3)GlcNAc, a substrate of AtFUC1. These results showed that AtFUC1 is an α1,3-fucosidase acting on plant complex-type N-glycans and elucidated the degradation pathway of plant complex-type N-glycans.

DOI： 10.1042/BCJ20170106

Skewing T helper cells exposed to asbestos fibers toward reduction of tumor immunity or activation of autoimmunity 査読

Kumagai-Takei N, Lee S, Matsuzaki H, Maeda M, Yu M, Sada N, Yoshitome K, Nishimura Y, Otsuki T

Kawasaki Med J 44 ( 4 ) 33 - 40 2018年

Glycoform of a newly identified pollen allergen, Cha o 3, from Chamaecyparis obtusa (Japanese cypress, Hinoki) 査読国際誌

Toshihiro Osada, Megumi Maeda, Chinatsu Tanabe, Kaori Furuta, Christopher J. Vavricka, Eiji Sasaki, Mitsuhiro Okano, Yoshinobu Kimura

CARBOHYDRATE RESEARCH 448 18 - 23 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

Cha o 3 is a newly found glycosylated allergen from Chamaecyparis obtusa (Japanese cypress) pollen. The deduced amino acid sequence of Cha o 3 indicates that this glycoallergen contains a cellulase domain and a number of putative N-glycosylation sites. However, the structures of N-glycans linked to Cha o 3 remain to be determined. In this study, therefore, we analyzed the glycoform of Cha o 3 and found that this glycoallergen carries exclusively plant complex-type N-glycans; major structures were G1cNAc2_ Man(3)Xyl(1)Fuc(1)GlcNAc(2) (39%), GaliFuciGlcNAc(2)Man(3)Xyl(1)FuciGlcNAc(2) (14%), and Gal(2)Fuc(2)G(1)cNAc2Man3. Xyl(1)Fuc(1)GIcNAc(2) (25%). The glycoform of Cha o 3 bearing the Lea epitope is similar to those of Cry j1, Jun a 1, or Cup a 1, major glycoallergens in cedar or cypress pollens, and the predominant occurrence of GIcNAc(2)Man3Xyl(1)Fuc(1)GIcNAc(2) is a common structural feature of glycoallergens from Cupressaceae pollens. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.carres.2017.05.005

Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos. 査読国際誌

Matsuzaki H, Kumagai-Takei N, Lee S, Maeda M, Sada N, Hatayama T, Yamamoto S, Ikeda M, Yoshitome K, Min Y, Nishimura Y, Otsuki T

Environmental health and preventive medicine 22 ( 1 ) 53 - 53 2017年6月

Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. 査読国際誌

Maeda M, Chen Y, Lee S, Kumagai-Takei N, Yoshitome K, Matsuzaki H, Yamamoto S, Hatayama T, Ikeda M, Nishimura Y, Otsuki T

International journal of oncology 50 ( 6 ) 2024 - 2032 2017年6月

Molecular characterization of tomato α1,3/4-fucosidase, a member of glycosyl hydrolase family 29 involved in the degradation of plant complex type N-glycans 査読国際誌

Md. Ziaur Rahman, Megumi Maeda, Satsuki Itano, Md. Anowar Hossain, Takeshi Ishimizu, Yoshinobu Kimura

Journal of Biochemistry 161 ( 5 ) 421 - 432 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press

In this study, we identified a gene in tomato that encodes an acidic α-fucosidase (LOC101254568 or Solyc03g006980, α-Fuc'ase S1-1), which may be involved in the turnover of plant complex-type N-glycans. Recombinant α-Fuc'ase S1-1 (rFuc'ase S1-1) was expressed using a baculovirus-insect cell expression system. rFuc'ase Sl-1 is 55 kDa in size and has an optimum pH around 4.5. It substantially hydrolyzed the non-reducing terminal α1,3-fucose residue on LNFP III and α1,4-fucose residues of Lea epitopes on plant complex-type N-glycans, but not the α1,2-fucose residue on LNFP I or the α1,3-fucose residue on pyridylaminated Fucα1-3GlcNAc. Furthermore, we found that this tomato α-Fuc'ase S1-1 was inactive toward the core penta-oligosaccharide unit [Manβ1-4(Xylβ1-2)GlcNAcβ1-4(Fucα1-3)GlcNAc-PA] of plant complex-type N-glycans. Molecular 3D modelling of α-Fuc'ase Sl-1 and structure/sequence interpretation based on comparison with a homologous a-fucosidase from Bifidobacterium longum subsp. infantis (Blon-2336) indicated that residues Asp193 and Glu237 might be important for substrate binding.

DOI： 10.1093/jb/mvw089

アスベスト長期曝露ヒト制御性T細胞株モデルにおける細胞周期の解析

大槻剛巳, 李順姫, 松崎秀紀, 武井直子, 吉留敬, 西村泰光, 前田恵

産業衛生学雑誌 59 ( 臨増 ) 505 - 505 2017年5月

Occurrence of complex type free N-glycans with a single GlcNAc residue at the reducing termini in the fresh-water plant, Egeria densa 査読国際誌

Megumi Maeda, Natsuki Ebara, Misato Tani, Christopher J. Vavricka, Yoshinobu Kimura

Glycoconjugate Journal 34 ( 2 ) 229 - 240 2017年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer New York LLC

In our previous study, we found unique free N-glycans (FNGs), which carry a single GlcNAc residue (GN1) at the reducing-end side and the Lewis-a epitope at the non-reducing-end side, in the culture broth of rice cells. Based on the FNG structural features and the substrate specificity of plant ENGase, we hypothesized that there might be a novel biosynthetic mechanism responsible for the production of these unique GN1-FNGs, in which high-mannose type (HMT)-GN1-FNGs produced in the cytosol from misfolded glycoproteins by ENGase are transported back into the endoplasmic reticulum and processed to plant complex type (PCT)-GN1-FNGs in the Golgi apparatus. Until now, however, PCT-GN1-FNGs had only been found in the culture broth of rice cultured cells and never in plants, suggesting that the formation of PCT-GN1-FNGs might be generated under special or artificial conditions. In this study, we confirm the presence of PCT-GN1-FNGs, HMT-GN1-FNGs and PCT-GN2-FNGs in the fresh-water plant Egeria densa. These results suggest that a mechanism responsible for the production of PCT-GN1-FNG is present in native plant tissues.

DOI： 10.1007/s10719-016-9758-z

Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers. 査読国際誌

Lee S, Matsuzaki H, Maeda M, Yamamoto S, Kumagai-Takei N, Hatayama T, Ikeda M, Yoshitome K, Nishimura Y, Otsuki T

International journal of oncology 50 ( 1 ) 66 - 74 2017年1月

Structural feature of N-glycans of bamboo shoot glycoproteins: useful source of plant antigenic N-glycans 査読国際誌

Chinatsu Tanabe, Kaori Furuta, Megumi Maeda, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 81 ( 7 ) 1405 - 1408 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

An effective method to prepare plant complex type (PCT) N-glycans in large amounts has been required to evaluate their immunological activity. In this study, we found that glycoproteins in bamboo shoots predominantly carry PCT N-glycans including the Lewis a epitope-containing ones, suggesting that bamboo shoot is an excellent source for the plant antigenic glycans to synthesize immunoactive neoglycopolymers.

DOI： 10.1080/09168451.2017.1320519

ヒトT細胞株への白石綿・青石綿継続曝露に伴う細胞特性の変化査読

李順姫, 前田恵, 松﨑秀紀, 武井直子, 山本祥子, 幡山圭代, 吉留敬, 西村泰光, 大槻剛巳

日本予防医学雑誌 10 ( 3 ) 119 - 125 2016年12月

健康増進住居環境の構築：マイナス帯電粒子優位室内環境によるナチュラル・キラー活性の増強査読

西村泰光, 高橋一聡, 小谷宗男, 間瀬昭則, 白濱毅, 前田恵, 李順姫, 松崎秀紀, 武井直子, 吉留敬, 阿見和久, 大槻剛巳

生存科学 26 ( 2 ) 181 - 190 2016年10月

珪酸粒子・アスベスト繊維の免疫影響査読

大槻剛巳, 李順姫, 前田恵, 林宏明, 松﨑秀紀, 武井直子, 吉留敬, 西村泰光

繊維状物質研究 3 4 - 11 2016年10月

FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line. 査読国際誌

Matsuzaki H, Lee S, Maeda M, Kumagai-Takei N, Nishimura Y, Otsuki T

Journal of immunotoxicology 13 ( 5 ) 620 - 7 2016年9月

Possible contribution of alpha2,6-sialylation to luteolysis in cows by inhibiting the luteotropic effects of galectin-1 査読国際誌

Kazuhisa Hashiba, Junko Nio-Kobayashi, Masahiro Sano, Megumi Maeda, Yoshinobu Kimura, Yuki Yamamoto, Koji Kimura, Kiyoshi Okuda

Biology of Reproduction 95 ( 1 ) 17 - 17 2016年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Society for the Study of Reproduction

The corpus luteum (CL) is essential for establishing pregnancy. If pregnancy does not occur during the estrous cycle, luteolysis is induced by prostaglandin (PG) F2alpha secreted from the uterus. Galectin-1, a beta-galactose-binding protein, is expressed in the functional CL of cows and increases the viability of bovine luteal steroidogenic cells (LSCs) by modifying the functions of membrane glycoproteins. The binding of galectin-1 to glycoproteins is blocked by alpha2,6-sialylation of the terminal galactose residues of glycoconjugates, which is catalyzed by a sialyltransferase (ST6Gal-I). However, the physiological role of alpha2,6-sialic acid in bovine CL is unclear. The level of alpha2,6-sialylation of the bovine CL was higher during the regressed-luteal stage than in other luteal stages. Lectin histochemistry revealed that alpha2,6-sialylated glycoconjugates were localized to luteal endothelial cells throughout the estrous cycle. In addition, alpha2,6-sialylated glycoconjugates concentrated to the membrane of LSCs during the regressed-luteal stage. PGF2alpha treatment for 72 h enhanced the expression of ST6Gal-I mRNA and the level of alpha2,6-sialylated glycoproteins in mid-LSCs. The level of alpha2,6-sialylated glycoproteins of late-stage LSCs (Days 15-17 after ovulation) was higher than that of mid-stage LSCs (Days 8-12 after ovulation), and galectin-1 increased the viability of mid-LSCs but not that of late-stage LSCs. Furthermore, galectin-1 increased the viability of late-LSCs when alpha2,6-sialic acid residues were removed by neuraminidase. The overall findings suggest that alpha2,6-sialylation stimulated by PGF2alpha contributes to luteolysis by inhibiting the luteotropic effects of galectin-1 in bovine CL.

DOI： 10.1095/biolreprod.116.140194

The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells. 査読国際誌

Yuho Maki, Yasumitsu Nishimura, Shinichi Toyooka, Junichi Soh, Kazunori Tsukuda, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoka, Tsuyoshi Ueno, Norimitsu Tanaka, Hiromasa Yamamoto, Hiroaki Asano, Megumi Maeda, Naoko Kumagai-Takei, Suni Lee, Hidenori Matsuzaki, Takemi Otsuki, Shinichiro Miyoshi

Oncology letters 11 ( 5 ) 3308 - 3316 2016年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.

DOI： 10.3892/ol.2016.4412

Rice alpha-fucosidase active against plant complex type N-glycans containing Lewis a epitope: purification and characterization 査読国際誌

Md. Ziaur Rahman, Makoto Fujishige, Megumi Maeda, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 ( 2 ) 291 - 294 2016年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

Rice -fucosidase (-fucosidase Os, 58kDa) that is active for 1-4 fucosyl linkage in Lewis a unit of plant N-glycans was purified to homogeneity. -fucosidase Os showed activity against 1-3 fucosyl linkage in Lacto-N-fucopentaose III but not 1-3 fucosyl linkage in the core of plant N-glycans. The N-terminal sequence of -fucosidase Os was identified as A-A-P-T-P-P-P-L-, and this sequence was found in the amino acid sequence of the putative rice -fucosidase 1 (Os04g0560400).

DOI： 10.1080/09168451.2015.1079479

Structural features of N-glycans linked to glycoproteins expressed in three kinds of water plants: Predominant occurrence of the plant complex type N-glycans bearing Lewis a epitope 査読国際誌

Megumi Maeda, Misato Tani, Takeo Yoshiie, Christopher J. Vavricka, Yoshinobu Kimura

Carbohydrate Research 435 50 - 57 2016年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier Ltd

The Japanese cedar pollen allergen (Cry j1) and the mountain cedar pollen allergen (Jun a1) are glycosylated with plant complex type N-glycans bearing Lewis a epitope(s) (Galβ1-3[Fucα1-4]GlcNAc-). The biological significance of Lewis a type plant N-glycans and their effects on the human immune system remain to be elucidated. Since a substantial amount of such plant specific N-glycans are required to evaluate immunological activity, we have searched for good plant-glycan sources to characterize Lewis a epitope-containing plant N-glycans. In this study, we have found that three water plants, Elodea nuttallii, Egeria densa, and Ceratophyllum demersum, produce glycoproteins bearing Lewis a units. Structural analysis of the N-glycans revealed that almost all glycoproteins expressed in these three water plants predominantly carry plant complex type N-glycans including the Lewis a type, suggesting that these water plants are good sources for preparation of Lewis a type plant N-glycans in substantial amounts.

DOI： 10.1016/j.carres.2016.09.008

ウシ黄体維持機構におけるepidermal growth factor receptorのcore fucosylationの役割

羽柴一久, 小林純子, 佐野栄宏, 前田恵, 木村吉伸, 奥田潔, 木村康二

日本繁殖生物学会講演要旨集 109 OR2-33 - OR2-33 2016年

記述言語：日本語出版者・発行元：公益社団法人日本繁殖生物学会

【目的】Epidermal growth factor receptor（EGFR）に結合するN型糖鎖上のcore fucoseは，epidermal growth factor（EGF）のEGFRへの結合に重要である。EGFは黄体細胞の生存を維持し，EGFRへの結合親和性は機能黄体において高いことから，黄体においてもEGFRの黄体維持作用にcore fucosylationの関与が考えられる。本研究では，1）発情周期を通じたウシ黄体のcore fucosylationレベルとfucose含有糖タンパク質の局在，2）黄体細胞のEGFR糖鎖のcore fucosylationの有無，3） EGFの黄体機能維持作用に及ぼすcore fucosylationの影響を検討した。【方法】1）発情周期を通じた黄体（初期：Days 2–3，形成期：Days 5–6，中期Days 8–12，後期：Days 15–17，退行期：Days 19–21）の膜画分のcore fucosylationレベルをfucoseを認識するAALレクチンを用いて検討し，fucose含有糖タンパク質の局在を解析した。2）中期黄体細胞から免疫沈降法によりEGFRタンパク質を回収後，core fucosylationの有無を調べた。3）中期黄体細胞にα-fucosidase（0.01，0.1 units/ml）を添加してcore fucoseを切断し，16時間後のcore fucosylationレベル，上清中のprogesterone（P4）濃度と生存率を検討した。黄体細胞にα-fucosidase（0.1 units/ml）とEGF（5，10 ng/ml）を単独又は組み合わせて添加し，24時間後のP4濃度と生存率を調べた。【結果】1）黄体の糖タンパク質のcore fucosylationレベルは後期，退行期と比較して，初期，形成期と中期に高く，fucose含有糖タンパク質は黄体細胞に局在した。2）黄体細胞のEGFR糖鎖はcore fucosylationを受けていた。3）黄体細胞の糖タンパク質のcore fucosylationレベルと生存率は，α-fucosidase添加区において減少し，P4産生に変化はなかった。EGFによる生存率の増加は，α-fucosidaseの共添加により減少し，P4産生に変化はなかった。以上より，EGFの黄体機能維持作用にEGFRのcore fucosylationが重要であり，core fucosylationの低下が黄体の構造的退行に関与する可能性が示された。

DOI： 10.14882/jrds.109.0_or2-33

Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos. 査読国際誌

Ying C, Maeda M, Nishimura Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Yoshitome K, Yamamoto S, Hatayama T, Otsuki T

Toxicology 338 86 - 94 2015年12月

Exposure to negatively charged-particle dominant air-conditions on human lymphocytes in vitro activates immunological responses. 査読国際誌

Nishimura Y, Takahashi K, Mase A, Kotani M, Ami K, Maeda M, Shirahama T, Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Otsuki T

Immunobiology 220 ( 12 ) 1359 - 68 2015年12月

T cell alteration caused by exposure to asbestos 査読

Megumi Maeda, Shoko Yamamoto, Tamayo Hatayama, Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Yasumitsu Nishimura, Yoshinobu Kimura, Takemi Otsuki

Biological Effects of Fibrous and Particulate Substances 195 - 210 2015年10月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

A model to examine the effects of continuous exposure to asbestos on human T cells was established to interpret experimental findings for clinical utilization. Although transient exposure causes apoptosis in the human polyclonal cell line MT-2, continuous and relatively low-dose exposure resulted in resistance against asbestos-induced apoptosis with a higher production of TGF-β and IL-10 and subsequent resistance to TGF-β-induced growth inhibition and activation of STAT3 and Bcl-2. These alterations caused by continuous exposure to chrysotile asbestos were also observed in a subline exposed continuously to crocidolite and included resistance to apoptosis, changes of cytokine production, and demonstration of the importance of Bcl-2 for resistance against apoptosis. In addition, analysis of protein expression among the MT-2 original cell line, which was never exposed to asbestos, and the continuously exposed subline showed the phosphorylation of β-actin and the increasing level of cytoskeletal molecules. These findings indicate the importance of the cytoskeleton as the initial contact site between cells and asbestos fibers, particularly fibers that cannot move into the inside of cells because of their physical features. Finally, the CXCR3 chemokine receptor and related antitumor cytokine IFN-γ were assayed in these sublines continuously exposed to asbestos, as well as in vitro stimulated freshly isolated peripheral CD4 T cells derived from healthy donors and exposed to asbestos fibers. The CXCR3 expression and production capacity for IFN-γ were reduced by asbestos exposure, and these findings were also confirmed for peripheral CD4 T cells derived from patients with pleural plaque and malignant mesothelioma. The overall findings observed in continuously exposed human T cell models will contribute towards the early detection of asbestos exposure and occurrence of mesothelioma using peripheral blood and will improve the immune status (reducing antitumor immunity in asbestos-exposed patients) through the use of certain physiological substances derived from plants, foods, and microorganisms.

DOI： 10.1007/978-4-431-55732-6_11

Effects of asbestos fibers on human cytotoxic T cells 査読

Naoko Kumagai-Takei, Yasumitsu Nishimura, Hidenori Matsuzaki, Megumi Maeda, Suni Lee, Kei Yoshitome, Takemi Otsuki

Biological Effects of Fibrous and Particulate Substances 211 - 221 2015年10月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

The immunological effects of asbestos have been demonstrated and include reduction of antitumor immunity such as the reduction of natural killer (NK) cell activity with decreased expression of NK cell-activating receptor, NKp46, as well as reduced expression of CXCR3, chemokine receptor, and interferon (IFN)-γ in CD4+ T cells. In this review, the effects of asbestos as demonstrated by our investigations on the cellular characteristics and functions of cytotoxic T lymphocytes (CTLs) differentiated from CD8+ T cells are shown and discussed. Experiments involving in vitro exposure of chrysotile asbestos onto a mixed lymphocyte reaction (MLR) assay to estimate clonal expansion (proliferation and differentiation) of CD8+ T cells revealed the inhibition of both proliferation and differentiation. These results should be interpreted as the impairment of CTL differentiation in the lymph nodes, where asbestos fibers are located continuously in asbestos-exposed people. In addition, analyses of cellular functions in asbestos-exposed patients with pleural plaque (PP) and malignant mesothelioma (MM) are discussed. PP patients showed an increase in effector memory CD8+ T cells compared to healthy donors or MM patients. Furthermore, MM patients showed a decrease in perforin-expressing CD8+ T cells. These results indicated that although asbestos-exposed individuals are ready to respond with transformed cells, CTLs may lose their function once mesothelioma progresses.

DOI： 10.1007/978-4-431-55732-6_12

beta-Galactosidase from Ginkgo biloba seeds active against beta-galactose-containing N-glycans: purification and characterization 査読国際誌

Md. Ziaur Rahman, Megumi Maeda, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 79 ( 9 ) 1464 - 1472 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

In this study, we purified an acidic beta-galactosidase to homogeneity from Ginkgo biloba seeds (beta-Gal'ase Gb-1) with approximately 270-fold purification. A molecular mass of the purified beta-Gal'ase Gb-1 was estimated about 35kDa by gel filtration and 32kDa by SDS-PAGE under non-reducing condition, respectively. On the other hand, beta-Gal'ase Gb-1 produced a single band with a molecular mass of 16kDa by SDS-PAGE under reducing condition. The N-terminal amino acid sequences of 32kDa and 16kDa molecules were the same and identified as H-K-A-N-X-V-T-V-A-F-V-M-T-Q-H-, suggesting that beta-Gal'ase Gb-1 may function as a homodimeric structure in vivo. When complex-type N-glycans containing beta-galactosyl residues were used as substrates, beta-Gal'ase Gb-1 showed substantial activity for beta 1-4 galactosyl residue and modest activity for beta 1-3 galactosyl residue with an optimum pH near 5.0. Based on these results, the involvement of beta-Gal'ase Gb-1 in the degradation of plant complex-type N-glycans is discussed.

DOI： 10.1080/09168451.2015.1034653

Synthesis of a novel glycopolymer carrying multivalent plant antigenic N-glycans. 査読

Maeda M, Takeda N, Kimura M, Kimura Y

Glycoconjugate Journal 32 ( 5 ) 193 2015年9月

Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene silencing 査読国際誌

Miki Yamamoto-Hino, Hideki Yoshida, Tomomi Ichimiya, Sho Sakamura, Megumi Maeda, Yoshinobu Kimura, Norihiko Sasaki, Kiyoko F. Aoki-Kinoshita, Akiko Kinoshita-Toyoda, Hidenao Toyoda, Ryu Ueda, Shoko Nishihara, Satoshi Goto

Genes to Cells 20 ( 6 ) 521 - 542 2015年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing Ltd

Glycan structures are synthesized by a series of reactions conducted by glycosylation-related (GR) proteins such as glycosyltransferases, glycan-modifying enzymes, and nucleotide-sugar transporters. For example, the common core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O-xylosyltransferase, β1,4-galactosyltransferase I, β1,3-galactosyltransferase II, and β1,3-glucuronyltransferase. This raises the possibility that functional impairment of GR proteins involved in synthesis of the same glycan might result in the same phenotypic abnormality. To examine this possibility, comprehensive silencing of genes encoding GR and proteoglycan core proteins was conducted in Drosophila. Drosophila GR candidate genes (125) were classified into five functional groups for synthesis of GAGs, N-linked, O-linked, Notch-related, and unknown glycans. Spatiotemporally regulated silencing caused a range of malformed phenotypes that fell into three types: extra veins, thick veins, and depigmentation. The clustered phenotypes reflected the biosynthetic pathways of GAGs, Fringe-dependent glycan on Notch, and glycans placed at or near nonreducing ends (herein termed terminal domains of glycans). Based on the phenotypic clustering, CG33145 was predicted to be involved in formation of terminal domains. Our further analysis showed that CG33145 exhibited galactosyltransferase activity in synthesis of terminal N-linked glycans. Phenotypic clustering, therefore, has potential for the functional prediction of novel GR genes.

DOI： 10.1111/gtc.12246

Identification of β1,3-galactosyltransferases responsible for biosynthesis of insect complex-type N-glycans containing a T-antigen unit in the honeybee 査読国際誌

Tomomi Ichimiya, Megumi Maeda, Shou Sakamura, Masato Kanazawa, Shoko Nishihara, Yoshinobu Kimura

Glycoconjugate Journal 32 ( 3-4 ) 141 - 151 2015年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Kluwer Academic Publishers

Honeybees (Apis mellifera) produce unique complex-type N-glycans bearing a Galβ1-3GalNAc (T-antigen) unit, and honeybee-specific N-glycans are linked to royal jelly glycoproteins. In this study, we identified two novel honeybee β1,3-galactosyltransferase (β1,3-GalT) genes responsible for biosynthesis of the T-antigen in insect N-glycans. The products of the two putative β1,3-GalT genes (β1,3-GalT1 and β1,3-GalT2), which were expressed in Sf21 insect cells, transferred galactose (Gal) residues to GalNAc2GlcNAc2Man3GlcNAc2-PA to form the Galβ1-3GalNAc unit, indicating that the identified genes were involved in biosynthesis of the β1-3 Gal-containing N-glycan. Therefore, using biochemistry and molecular biology techniques, we revealed a unique N-glycan biosynthesis mechanism in the cephalic region of honeybees, which has not previously been found in other animal or plant cells.

DOI： 10.1007/s10719-015-9585-7

抗腫瘍免疫への石綿曝露影響査読

武井直子, 西村泰光, 前田恵, 林宏明, 松崎秀紀, 李順姫, 吉留敬, 岸本卓巳, 福岡和也, 中野孝司, 大槻剛巳

日本予防医学会雑誌 10 ( 1 ) 1 - 8 2015年4月

Enhancement of NK Cell Cytotoxicity Induced by Long-Term Living in Negatively Charged-Particle Dominant Indoor Air-Conditions. 査読国際誌

Nishimura Y, Takahashi K, Mase A, Kotani M, Ami K, Maeda M, Shirahama T, Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Otsuki T

PloS one 10 ( 7 ) e0132373 2015年

Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients. 査読国際誌

Nishimura Y, Kumagai-Takei N, Matsuzaki H, Lee S, Maeda M, Kishimoto T, Fukuoka K, Nakano T, Otsuki T

BioMed research international 2015 238431 - 238431 2015年

Cloning and expression analysis of acidic peptide:N-glycanase genes in Solanum lycoperisicum. 査読

Fujikawa, M, Maeda, M, Fujiyama , K, Kimura, Y

Glycoconjugate Journal 32 ( 5 ) 193 2015年

Purification and characterization of Ginkgo biloba α-1,3/4-fucosidase active against Lewis a antigen 査読

Itano, S, Maeda, M, Kimura, Y

Glycoconjugate Journal 32 ( 5 ) 195 2015年

Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2. 査読国際誌

Maeda M, Chen Y, Hayashi H, Kumagai-Takei N, Matsuzaki H, Lee S, Nishimura Y, Otsuki T

International journal of oncology 45 ( 6 ) 2522 - 32 2014年12月

【レギュラトリーT細胞の機能発現】制御性T細胞機能へのアスベスト曝露影響査読

西村泰光, 三浦由恵, 前田恵, 松崎秀紀, 李順姫, 武井直子, 大槻剛巳

剛巳【レギュラトリーT細胞の機能発現】制御性T細胞機能へのアスベスト曝露影響 (解説/特集) 臨床免疫・アレルギー科 62 ( 4 ) 366 - 370 2014年10月

Silica exposure and altered regulation of autoimmunity. 査読国際誌

Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Maeda M, Chen Y, Kusaka M, Urakami K, Hayashi H, Fujimoto W, Nishimura Y, Otsuki T

Environmental health and preventive medicine 19 ( 5 ) 322 - 9 2014年9月

アスベスト曝露によるTh1細胞機能の低下査読

西村泰光, 前田恵, 三浦由恵, 松崎秀樹, 李順姫, 武井直子, 大槻剛巳

.臨床免疫・アレルギー科 62 ( 3 ) 314 - 317 2014年9月

珪酸曝露による免疫影響査読

松﨑秀紀, 前田恵, 林宏明, 武井直子, 李順姫, 吉留敬, 草加勝康, 浦上更三, 西村泰光, 兵藤文則, 大槻剛巳

日本予防医学会雑誌 9 ( 1 ) 1 - 8 2014年4月

Large-scale preparation of glycopeptides harboring the TF-antigen unit from royal jelly 査読国際誌

Megumi Maeda, Tatsuya Tanaka, Mariko Kimura, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 ( 2 ) 276 - 278 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

We have reported that new N-glycans carrying the TF-antigen occurred on a major royal jelly glycoprotein, and we have identified the glycosylation site to which the antigenic N-glycan is linked, but an appropriate procedure has not been established to prepare non-labeled immunoreactive glycopeptides in large amounts for functional analysis. In this study, we developed an effective method of preparing Asn-glycopeptide bearing TF-antigen.

DOI： 10.1080/09168451.2014.878223

Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma. 査読国際誌

Kumagai-Takei N, Nishimura Y, au, Maeda M, Hayashi H, Matsuzaki H, Lee S, Kishimoto T, Fukuoka K, Nakano T, Otsuki T

Journal of immunology research 2014 670140 - 670140 2014年

珪肺症例における自己寛容破綻の異常

大槻剛巳, 前田恵, 松崎秀紀, 李順姫, 武井直子, 西村泰光

日本毒性学会学術年会 41.1 O-39 2014年

記述言語：日本語出版者・発行元：日本毒性学会

珪酸とアスベストの慢性職業性曝露は塵肺症として知られる肺の繊維化を惹起する。珪酸曝露症例は珪肺症と呼ばれるが，合併症として強皮症，関節リウマチ（Caplan症候群として知られる），ANCA関連血管炎などの自己免疫疾患が知られている。従来，珪酸のアジュバントとしての作用と捉えられてきたが，我々は，珪酸曝露が直接免疫系に対して，なんらかの影響（毒性あるいは活性化）を惹起する可能性を考えて，実験系あるいは症例の末梢血単核球や，リンパ球などを用いて検討を加えてきた。アスベストについては，悪性中皮腫や肺癌などの悪性腫瘍の合併が知られており，この観点でもアスベストによる免疫系への毒性としての，腫瘍免疫の減衰について，いくつかの知見を得ているが，本演題では珪酸の免疫担当細胞への影響について，報告する。まずリンパ球の細胞死に関連が深いCD95/Fas分子について，可溶性Fasやその他のFas媒介アポトーシス阻害因子が珪肺症例で上昇していること。一方，機能性抗Fas自己抗体の検出や内因性生理的Fas誘導アポトーシスの阻害因子の珪肺症例末梢血単核球での発現減弱などの所見より，珪肺症例では慢性活性化を受け，長期生存にいたり，おそらくは自己抗原とも反応している一群と，細胞死に陥ってはリクルートされている一群がある可能性が想起された。前者は，反応性T細胞で，その他可溶性IL-2受容体の血清中での上昇や，Decoy Receptor 3 (DcR3)分子の血漿中濃度上昇，PD-1 mRNAの発現上昇などの活性化指標が検出された。一方，後者は制御性T細胞の可能性があり，珪肺症例制御性T細胞では活性化に伴うFas分子の過剰発現とともに，早期の細胞死が誘導されることが観察された。これらの免疫バランスの異常が，珪肺症例での自己寛容の破綻を惹起している可能性がある。

DOI： 10.14869/toxpt.41.1.0_o-39

Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos. 査読国際誌

Maeda M, Chen Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Hiratsuka J, Nishimura Y, Kimura Y, Otsuki T

Immunobiology 218 ( 9 ) 1184 - 91 2013年9月

Purification and Substrate Specificity of A Ginkgo biloba Glycosidase Active in beta-1,2-Xylosidic Linkage in Plant Complex Type N-Glycans 査読国際誌

Megumi Maeda, Tsuyoshi Akiyama, Daisuke Yokouchi, Kwan Kit Woo, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 77 ( 9 ) 1973 - 1976 2013年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

The beta-xylosidase, which is active against plant complex type N-glycans, was purified to homogeneity from Ginkgo biloba seeds. The N-terminal amino acid sequence, G-S-A-A-G-N-R-, of the Ginkgo beta-xylosidase (beta-Xyl'ase Gb) was consistent with the deduced internal amino acid sequence of an Arabidopsis beta-xylosidase (AtBXL1). beta-Xyl'ase Gb hydrolyzed the beta 1-2 xylosyl residue from Xyl beta 1-2Man beta 1-4G1cNAc beta 1-4GlcNAc-PA and Xyl beta 1-2Man beta 1-4G1cNA beta 1-4(Fuc alpha 1-3)GlcNAc-PA, but not that from Manal-6(Man alpha 1-3)(Xy1 beta 1-2)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-3)GlcNAc-PA.

DOI： 10.1271/bbb.130303

Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in mixed lymphocyte reaction of human peripheral blood mononuclear cells. 査読国際誌

Kumagai-Takei N, Nishimura Y, au, Maeda M, Hayashi H, Matsuzaki H, Lee S, Hiratsuka J, Otsuki T

American journal of respiratory cell and molecular biology 49 ( 1 ) 28 - 36 2013年7月

Purification and characterization of beta-xylosidase that is active for plant complex type N-glycans from tomato (Solanum lycopersicum): removal of core alpha 1-3 mannosyl residue is prerequisite for hydrolysis of beta 1-2 xylosyl residue 査読国際誌

Daisuke Yokouchi, Natsuko Ono, Kosuke Nakamura, Megumi Maeda, Yoshinobu Kimura

GLYCOCONJUGATE JOURNAL 30 ( 5 ) 463 - 472 2013年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

In this study, we purified and characterized the beta-xylosidase involved in the turnover of plant complex type N-glycans to homogeneity from mature red tomatoes. Purified beta-xylosidase (beta-Xyl'ase Le-1) gave a single band with molecular masses of 67 kDa on SDS-PAGE under a reducing condition and 60 kDa on gelfiltration, indicating that beta-Xyl'ase Le-1 has a monomeric structure in plant cells. The N-terminal amino acid could not be identified owing to a chemical modification. When pyridylaminated (PA-) N-glycans were used as substrates, beta-Xyl'ase Le-1 showed optimum activity at about pH 5 at 40 A degrees C, suggesting that the enzyme functions in a rather acidic circumstance such as in the vacuole or cell wall. beta-Xyl'ase Le-1 hydrolyzed the beta 1-2 xylosyl residue from Man(1)Xyl(1)GlcNAc(2)-PA, Man(1)Xyl(1)Fuc(1)GlcNAc(2)-PA, and Man(2)Xyl(1)Fuc(1)GlcNAc(2)-PA, but not that from Man(3)Xyl(1)GlcNAc(2)-PA or Man(3)Xyl(1)Fuc(1)GlcNAc(2)-PA, indicating that the alpha 1-3 arm mannosyl residue exerts significant steric hindrance for the access of beta-Xyl'ase Le-1 to the xylosyl residue, whereas the alpha 1-3 fucosyl residue exerts little effect. These results suggest that the release of the beta 1-2 xylosyl residue by beta-Xyl'ase Le-1 occurs at least after the removal the alpha-1,3-mannosyl residue in the core trimannosyl unit.

DOI： 10.1007/s10719-012-9441-y

Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases. 査読国際誌

Nishimura Y, Maeda M, Kumagai-Takei N, Lee S, Matsuzaki H, Wada Y, Nishiike-Wada T, Iguchi H, Otsuki T

Environmental health and preventive medicine 18 ( 3 ) 198 - 204 2013年5月

Exploration of biomarkers for asbestos exposure and occurrence of malignant mesothelioma based on the immunological effects of asbestos.

Matsuzaki H, Lee S, Kumagai-Takei N, Hayashi H, Miura Y, Chen Y, Maeda M, Yamamoto S, Hatayama T, Nishimura Y, Otsuki T

Journal of Data Mining Genomics Proteomics S2 001 2013年

アスベストの免疫毒性学的側面と病態への関与

大槻剛巳, 前田恵, 武井直子, 松崎秀紀, 李順姫, 西村泰光

日本毒性学会学術年会 40.1 1114 2013年

記述言語：日本語出版者・発行元：日本毒性学会

アスベストによる発癌性については，含有する鉄による酸化ストレス，繊維状物質としての物理的なDNA損傷，そしてその他の発癌物質の吸着などが考えられる。一方，アスベストは珪酸（SiO2)の金属塩であり，珪酸曝露症例（珪肺症）にて自己免疫疾患が多く合併することや，その実験的検証から，アスベストもまた免疫毒性あるいは免疫担当細胞への作用が想定される。さらにアスベスト曝露者の合併症として悪性中皮腫などの発癌，初期曝露からの長期の潜伏期を考えると，抗腫瘍免疫の減衰などを惹起している可能性がある。我々は，アスベストの免疫担当細胞への影響ならびに抗腫瘍免疫との関連について，検討を加えている。細胞株モデル，健常人末梢血から採取した新鮮免疫担当細胞，あるいは曝露者（胸膜プラークや悪性中皮腫症例）の末梢血のリンパ球の解析を行ってきている。T細胞では，細胞株や，健常人由来細胞にて長期曝露によってアスベストが誘導するアポトーシスに抵抗性を獲得することが判明し，その機序として，Src-kinase，IL-10，STAT3，BCL-2の関与が判明した。さらにこれらの細胞では，抗腫瘍免疫にも重要なCXCR3発現やIFNγ産生の低下も認められた。制御性T細胞では細胞株モデルにて可用性因子であるIL-10，TGFβの産生過剰とともに細胞間接着による反応性T細胞の活性化抑制能の増強も確認された。制御性T細胞ではマスタージーンであるFoxP3を制御するFOXO1の発現低下と，それに伴う細胞周期の異調節なども観察されている。また，CD8+細胞障害性T細胞においても，実験系での分化誘導・増殖時のアスベスト曝露での抑制が判明した。一方，NK細胞においても，細胞内シグナリングの減弱とともに，機能発現活性化受容体の発現減弱が認められ，特にNKp46分子については，アスベスト曝露症例においても，その殺細胞能との相関が認められた。さらなる検討とともに，曝露や担癌の指標あるいは予防的観点からのこれらの成果の応用も期待される。

DOI： 10.14869/toxpt.40.1.0.1114.0

Structural features of N-glycans of seaweed glycoproteins: predominant occurrence of high-mannose type N-glycans in marine plants. 査読国際誌

Yoshiie T, Maeda M, Kimura M, Hama Y, Uchida M, Kimura Y

Bioscience, biotechnology, and biochemistry 76 ( 10 ) 1996 - 1998 2012年10月

Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell. 査読国際誌

Maeda M, Yamamoto S, Chen Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Hatayama T, Miyahara N, Katoh M, Hiratsuka J, Nishimura Y, Otsuki T

The Science of the total environment 429 174 - 82 2012年7月

Environmental factors producing autoimmune dysregulation--chronic activation of T cells caused by silica exposure. 査読国際誌

Lee S, Hayashi H, Maeda M, Chen Y, Matsuzaki H, Takei-Kumagai N, Nishimura Y, Fujimoto W, Otsuki T

Immunobiology 217 ( 7 ) 743 - 8 2012年7月

Review of reduced tumor immunity caused by asbestos exposure to immunocompetent cells such as T and NK cells. 査読

Otsuki T, Lee S, Kumagai-Takei N, Miyahara N, Katoh M, Yamamoto S, Hatayama T, Matsuzaki H, Nishimura Y, Maeda M, Hayashi H, Hirastuka J, Chen Y

Open Access Scientific reports 1 ( 8 ) open access 2012年

Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis. 査読国際誌

Matsuzaki H, Maeda M, Lee S, Nishimura Y, Kumagai-Takei N, Hayashi H, Yamamoto S, Hatayama T, Kojima Y, Tabata R, Kishimoto T, Hiratsuka J, Otsuki T

Journal of biomedicine & biotechnology 2012 492608 - 492608 2012年

Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients. 査読国際誌

Megumi Maeda, Yasumitsu Nishimura, Hiroaki Hayashi, Naoko Kumagai, Ying Chen, Shuko Murakami, Yoshie Miura, Jun-ichi Hiratsuka, Takumi Kishimoto, Takemi Otsuki

American journal of respiratory cell and molecular biology 45 ( 4 ) 795 - 803 2011年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Asbestos causes malignant tumors such as lung cancer and malignant mesothelioma (MM). To determine whether asbestos exposure causes reduction of antitumor immunity, we established an in vitro T-cell line model of low-dose and continuous exposure to asbestos using an human adult T-cell leukemia virus-1 immortalized human polyclonal T-cell line, MT-2, and revealed that MT-2 cells exposed continuously to asbestos showed resistance to asbestos-induced apoptosis. In addition, the cells presented reduction of surface CXCR3 chemokine receptor expression and IFN-γ production. In this study, to confirm that these findings are suitable for clinical translation, surface CXCR3 and IFN-γ expression were analyzed using freshly isolated human CD4(+) T cells derived from healthy donors and patients with pleural plaque (PP) or MM. The results revealed that CXCR3 and IFN-γ expression in the ex vivo model were reduced in some cases. Additionally, CXCR3 expression in CD4(+) T cells from PPs and MMs was significantly reduced compared with that from healthy donors, and CD4(+) T cells from patients with MMs exhibited a marked reduction in IFN-γ mRNA levels after stimulation in vitro. Moreover, CD4(+)CXCR3(+) T cells in lymphocytes from MMs showed a tendency for an inverse correlation with its ligand CXCL10/IP10 in plasma. These findings show reduction of antitumor immune function in asbestos-exposed patients and indicate that CXCR3, IFN-γ, and CXCL10/IP10 may be candidates to detect and monitor disease status.

DOI： 10.1165/rcmb.2010-0435OC

川崎医科大学における大学連携、産学官連携等、対外活動について：その2

大槻剛巳, 小笠原康夫, 柏原直樹, 佐藤稔, 大澤裕, 矢田豊隆, 毛利聡, 山内明, 武井直子, 前田恵, 西村泰光, 小野寺昇, 望月精一, 茅野功, 川西礼美, 福永仁夫

川崎医学会誌 37 47 - 59 2011年9月

Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2. 査読国際誌

Megumi Maeda, Yasumitsu Nishimura, Hiroaki Hayashi, Naoko Kumagai, Ying Chen, Shuko Murakami, Yoshie Miura, Jun-ichi Hiratsuka, Takumi Kishimoto, Takemi Otsuki

American journal of respiratory cell and molecular biology 45 ( 3 ) 470 - 9 2011年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.

DOI： 10.1165/rcmb.2010-0213OC

Effects of environmental substance on the human immune system - Reduction of tumor immunity induced by asbestos exposure

Naoko Kumagai, Megumi Maeda, Hidenori Matsuzaki, Suni Lee, Yasumitsu Nishimura, Takemi Otsuki

Biotherapy 25 ( 4 ) 739 - 746 2011年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Similar to the silica which causes dysregulation of autoimmunity as well as pulmonary fibrosis, asbestos, which is mineral silicate including iron, magnesium or calcium attached to the core silica molecule, SiO2 may affect the human immune system. Considering malignant complications of asbestos-exposed patients such as mesothelioma and lung cancer, asbestos is assumed to lower tumor immunity. The effects of asbestos on tumor immunity have been investigated with this in mind. It was found that natural killer (NK) cell activity was reduced in correspondence with the surface expression level of NKp46, one of the activating receptors of the NK cell. The proliferation and differentiation of cytotoxic T lymphocytes (CTL) were inhibited during induction of effector/memory CTL from naïve CD8+ T cells by culturing with allo-antigen supplemented with chrysotile-asbestos. In addition, tumor immunity-related molecules such as interferon (IFN) -γ and the CXCR3 chemokine receptor, were reduced by asbestos exposure using the T cell line, MT-2. Furthermore, activation-inhibitory functions such as the CD4 +CD25+FoxP3+ regulatory T cell possessing the MT-2 cell line, was enhanced by asbestos exposure. All of these findings suggested that asbestos exposure lowered tumor immunity. In addition, some of these findings were confirmed in asbestos-exposed patients. Reduction of tumor immunity caused by exposure to asbestos may make it easier to develop asbestos-inducing malignant tumors in the patients with asbestos exposure.

Quick detection of overexpressed genes caused by myeloma-specific chromosomal translocations using multiplex RT-PCR. 査読国際誌

San San Htwe, Megumi Maeda, Rui Matsumoto, Natsumi Sakamoto, Shuko Murakami, Shoko Yamamoto, Minako Katoh, Naoko Kumagai, Hiroaki Hayashi, Yasumitsu Nishimura, Mitsugi Ohkura, Hideho Wada, Masafumi Taniwaki, Takashi Sugihara, Takemi Otsuki

International journal of molecular medicine 27 ( 6 ) 789 - 94 2011年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Multiple myeloma (MM) is a malignancy of the plasmocyte and is associated with various symptoms such as anemia, immunodeficiency, bone lesions and kidney insufficiency. Although prognosis was poor until some years ago, recent advances that introduced newer molecular targeting agents such as bortezomib and thalidomide have resulted in a better prognosis for MM. However, clinical manifestations and the relationship between cellular and molecular findings, including chromosomal translocation and the related overexpression of oncogenes such as CCND1 (cyclin D1) and FGFR3 (fibroblast growth factor receptor 3), remain unclear. It has been reported that a specific translocation may influence the prognosis of MM. Although translocations and overexpressed genes should be examined in ordinary clinical investigations, limited definitive assays for translocation involve the use of FISH (fluorescent in situ hybridization) or SKY (special karyotypic) methods. We therefore, attempted to establish a quick detection method for major translocated genes such as FGFR3, CCND1, CCND3 and MAF using multiplex RT-PCR (MP-RT-PCR). MP-RT-PCR can be performed within several to 24 h after bone marrow samples are taken. Two of 21 bone marrow blood samples from MM patients were analyzed using MP-RT-PCR and double-color FISH, and the results of both methods were compatible. Future utilization and elaboration of this method may help our understanding of the cell biology and clinical features of MM.

DOI： 10.3892/ijmm.2011.648

珪酸の免疫影響と自己寛容の破綻査読

李順姫, 林宏明, 前田恵, 熊谷直子, 松﨑秀紀, 草加勝康, 浦上更三, 藤本亘, 大槻剛巳

臨床環境医学 20 40 - 53 2011年6月

Double-Knockout of Putative Endo-beta-N-acetylglucosaminidase (ENGase) Genes in Arabidopsis thaliana: Loss of ENGase Activity Induced Accumulation of High-Mannose Type Free N-Glycans Bearing N,N '-Acetylchitobiosyl Unit 査読国際誌

Yoshinobu Kimura, Yuki Takeoka, Masami Inoue, Megumi Maeda, Kazuhito Fujiyama

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 75 ( 5 ) 1019 - 1021 2011年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

Endo-beta-N-acetylglucosaminidase (ENGase) is involved in the production of high-mannose type free N-glycans during plant development and fruit maturation. In a previous study (K. Nakamura et al. Biosci. Biotechnol. Biochem., 73, 461-464 (2009)), we identified the tomato ENGase gene and found that gene expression remained relatively constant. In the present study, we constructed an Arabidopsis thaliana mutant in which the expression of two putative ENGase genes was suppressed. The mutant showed no ENGase activity, but produced high-mannose type free N-glycans carrying the N,N'-acetylchitobiosyl unit that is produced by peptide:N-glycanase, indicating that both these genes encode Arabidopsis ENGase.

DOI： 10.1271/bbb.110148

ヒト免疫担当細胞への環境中物質の影響―アスベスト曝露による腫瘍免疫減衰― 査読

熊谷直子, 前田恵, 松﨑秀紀, 李順姫, 西村泰光, 大槻剛巳

Biotherapy 25 ( 4 ) 739 - 746 2011年4月

Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients 査読

Otsuki T, Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Urakami K

Int J Immunopath Pharmacol 24 ( 1S ) 11S - 16S 2011年1月

Suppressive effect of asbestos on cytotoxicity of human NK cells 査読

Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, Nakano T, Miura Y, Hiratsuka J, Otsuki T

Int J Immunopath Pharmacol 24 ( 1S ) 5S - 10S 2011年1月

Asbestos induces reduction of tumor immunity. 査読国際誌

Kumagai-Takei N, Maeda M, Chen Y, Matsuzaki H, Lee S, Nishimura Y, Hiratsuka J, Otsuki T

Clinical & developmental immunology 2011 481439 - 481439 2011年

Structural features and Immunological activity of N-glycans of seaweed glyco- proteins. 査読

Yoshiie T, Maeda M, Kimura M, Kimura Y

Glycoconjugate Journal 28 ( 5 ) 2011年

Establishment of negatively-charged indoor air conditions and their biological effects

Takemi Otsuki, Kazuaki Takahashi, Akinori Mase, Takashi Kawado, Muneo Kotani, Yasumitsu Nishimura, Megumi Maeda, Shuko Murakami, Naoko Kumagai, Hiroaki Hayashi, Ying Chen, Yoshie Miura, Takashi Shirahama, Michiharu Yoshimatsu, Kanehisa Morimoto

Buildings and the Environment 201 - 214 2010年12月

Indoor air condition may be involved to the health status. Among various factors inindoor air conditions, few reports were published concerning negatively chargedparticles.In this review, we detaile the biological effects of negatively-charged indoorair conditions, particularly on the psycho-neuro-endocrino-immune network. The short-term (2.5 hours) and mmedium-term (2 weeks) abidance of negatively-charged airparticle dominant room resulted activation of natural killer cell activity induced byrecurrent transient activation of interleukin 2. These results indicate that negativelychargedindoor air condition is better for immune status and may improve daily lives. © 2009 Nova Science Publishers, Inc. All rights reserved.

Dysregulation of the immune system caused by silica and asbestos. 査読

Maeda M, Nishimura Y, Kumagai N, Hayashi H, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Hirastuka J, Otsuki T

Journal of immunotoxicology 7 ( 4 ) 268 - 278 2010年10月

珪酸・アスベストの免疫影響（ミニ特集：繊維･粒子状物質研究会（仙台））査読

熊谷直子, 西村泰光, 前田恵, 林宏明, 大槻剛巳

日本衛生学雑誌 64 ( 4 ) 493 - 499 2010年10月

[Immunological effects of silica/asbestos]. 査読

Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T

Nihon eiseigaku zasshi. Japanese journal of hygiene 65 ( 4 ) 493 - 9 2010年9月

Intracellular and extracellular free N-glycans produced by plant cells: Occurrence of unusual plant complex-type free N-glycans in extracellular speces. 査読国際誌

Maeda M, Kimura M, Kimura Y

J. Biocem. 148 ( 6 ) 681 - 692 2010年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

植物細胞の新生たんぱく質の品質管理系における脱グリコシル化機構を明らかにする目的で、イネ培養細胞が産生する遊離型Ｎ－グリカンの構造特性解析を行った。得られた結果は、これまでに知られていない新たな糖鎖遊離機構が存在することを示唆するものであった。

DOI： 10.1093/jb/mvq102

珪肺症例における自己免疫異常の検出血清可溶性インターロイキン2受容体と可溶性CD40リガンドの濃度の意義

林宏明, 西村泰光, 前田恵, 熊谷直子, 村上周子, 三浦由恵, 草加勝康, 浦上更三, 大槻剛巳

日本職業・災害医学会会誌 58 ( 2 ) 45 - 51 2010年3月

記述言語：日本語出版者・発行元：(一社)日本職業・災害医学会

珪肺症例では肺病変のみならず自己寛容の破綻が生じ、慢性関節リウマチや強皮症の合併が知られている。これらの自己免疫異常の血清学的な指標として可溶性インターロイキン2受容体(sIL-2R)や可溶性CD40リガンド(sCD40L)が有用かどうかを健常人、珪肺症例、強皮症症例で検討した結果を総括して、珪酸の制御性T細胞や活性化T細胞など、自己寛容の破綻に関連する細胞群への影響について概説する。(著者抄録)

その他リンク： http://search.jamas.or.jp/link/ui/2010218223

Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in silicosis patients. 査読

H. Hayashi, Y. Miura, M. Maeda, S. Murakami, N. Kumagai, Y. Nishimura, M. Kusaka, K. Urakami, W. Fujimoto, T. Otsuki

International journal of immunopathology and pharmacology 23 1099 - 1109 2010年1月

Causal links have been documented between silica and rheumatoid arthritis, lupus erythematosus, systemic sclerosis and glomerulonephritis. Two different effects of silica have been suggested, an enhanced inflammatory response in the pulmonary region (e.g. activation of alveolar macrophages) and dysregulation of autoimmunity. Based on our previous reports showing in vitro activation of peripheral T cells by silica and reduced regulatory function of the peripheral CD4(+)CD25(+) fraction in which FoxP(3)+ regulatory T cells (Treg) are located, reconstitution of the CD4(+)CD25(+) fraction in silicosis patients (SILs) was investigated. Since T cells in peripheral CD4(+)CD25(+) and CD4(+)CD25(-) (effector T cells; Teff) fractions from SILs showed higher expression of pd-1 (a marker gene for T cell activation) in comparison to that of healthy donors (HDs), chronic T cell activation was considered to have occurred in SILs. In this study, a higher expression of the CD95/Fas molecule in Treg was recorded from silicosis patients (SILs) compared to healthy donors (HDs), and excess loss of FoxP3(+) Treg in freshly isolated peripheral blood mononuclear cells (PBMCs) from SILs relative to HDs was demonstrated when these cells were cultured with silica ex vivo, whereas CD25(+) cells were not reduced due to contamination of activated Teff in the CD4(+)CD25(+) fraction. The activation of both Teff and Treg results in reconstitution of the peripheral CD4(+)CD25(+) fraction, loss of Treg and contamination of activated Teff, resulting in reduction of the number and function of Treg. These results contribute to our understanding of the development of autoimmune diseases found in SILs.

DOI： 10.1177/039463201002300414

Is soluble CD40 ligand an indicator of immunopathological disturbance in silicosis patients? 査読

HAYASHI Hiroaki, NISHIMURA Yasumitsu, MAEDA Megumi, MURAKAMI Shuko, KUMAGAI Naoko, CHEN Ying, KUSAKA Masayasu, URAKAMI Kozo, FUJIMOTO Wataru, OTSUKI Takemi

川崎医学会誌 35 ( 2 ) 129 - 138 2009年12月

The biological effects of negatively-charged indoor air conditions 査読

OTSUKI Takemi, TAKAHASHI Kazuaki, MASE Akinori, KAWADO Takashi, KOTANI Muneo, MAEDA Megumi, MURAKAMI Shuko, KUMAGAI Naoko, HAYASHI Hiroaki, CHEN Ying, NISHIMURA Yasumitsu, MIURA Yoshie, SHIRAHAMA Takashi, YOSHIMATSU Michiharu, MORIMOTO Kanehisa

川崎医学会誌 35 ( 3 ) 205 - 214 2009年10月

Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases. 査読国際誌

Shuko Murakami, Yasumitsu Nishimura, Megumi Maeda, Naoko Kumagai, Hiroaki Hayashi, Ying Chen, Masayasu Kusaka, Takumi Kishimoto, Takemi Otsuki

Environmental health and preventive medicine 14 ( 4 ) 216 - 22 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

This review is partly composed of the presentation "Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases" delivered during the symposium "Biological effects of fibrous and particulate substances and related areas" organized by the Study Group of Fibrous and Particulate Studies of the Japanese Society of Hygiene and held at the 78th Annual Meeting in Kumamoto, Japan. In this review, we briefly introduce the results of recent immunological analysis using the plasma of silica and asbestos-exposed patients diagnosed with silicosis, pleural plaque, or malignant mesothelioma. Thereafter, experimental background and speculation concerning the immunological pathophysiology of silica and asbestos-exposed patients are discussed.

DOI： 10.1007/s12199-008-0063-8

マイナス荷電粒子優位な室内空気環境の生体影響の観察精神・神経・内分泌・免疫ネットワークへの影響について

西村泰光, 高橋一聡, 間瀬昭則, 河戸隆, 小谷宗男, 阿見和久, 松島弘樹, 白濱毅, 吉松道晴, 前田恵, 村上周子, 林宏明, 熊谷直子, 陳瑩, 三浦由恵, 森本謙曩, 大槻剛巳

日本職業・環境アレルギー学会雑誌 16 ( 2 ) 15 - 24 2009年5月

記述言語：日本語出版者・発行元：日本職業・環境アレルギー学会

室内環境によって相互に関連する精神、神経、内分泌ならびに免疫の相互作用(PNEI(psycho-neuro-endocrino-immune)-ネットワーク)に影響するシックハウス症候群や化学物質過敏症が知られているが、室内環境の改善は健康増進という観点からも重要である。マイナス荷電粒子優位な室内環境を構築し、そのPNEIネットワークに及ぼす影響を検討したところ、時間単位の短期滞在試験では血清IL-2の上昇、週単位の中期滞在試験ではNK細胞の活性化が認められた。ストレス指標などには顕著な影響は認められなかったが、悪影響もなく今後月〜年単位の長期居住の影響あるいは細胞や遺伝子レベルへの影響の検討も興味深いと考えられた。また、森林浴などの健康効果の一部にもマイナス荷電粒子の影響が及んでいることも想定された。(著者抄録)

Two weeks of permanence in negatively-charged air conditions causes alteration of natural killer cell function 査読

K. Takahashi, Takemi Otsuki, Takemi Otsuki, A. Mase, T. Kawado, M. Kotani, Y. Nishimura, M. Maeda, S. Murakami, N. Kumagai, H. Hayashi, Y. Chen, T. Shirahama, Y. Miura, K. Morimoto

International Journal of Immunopathology and Pharmacology 22 333 - 342 2009年1月

掲載種別：研究論文（学術雑誌）

The effects of negatively-charged air conditions were analyzed as one of the approaches to improve health and quality of life. We previously reported that the use of a charcoal coating and application of an electric voltage yielded predominantly negatively-charged particles in an experimental room, and that 2.5 hours of living in these conditions caused a slight activation of the immune system (slight elevation of serum interleukin (IL)-2), regulated blood flow, and stabilized the autonomic nervous system when compared with control conditions (no dominance of negatively-charged particles). In this study, we expanded the previous study and placed 15 subjects in negatively-charged air conditions for two weeks during the night and analyzed various biological parameters. Although individual biological reactions differed from subject to subject, natural killer (NK) cell activity increased significantly following living in negatively-charged air conditions. Taken together, the results of the previous investigation and those of this study show that repeated elevation of IL-2 (although it immediately returned to the baseline level) causes chronic and recurrent stimulation to NK cells and results in the steady activation of NK cells. Negatively-charged air particles may be a good tool to improve health and quality of life. Copyright © by Biolife, s.a.s.

DOI： 10.1177/039463200902200210

Effects of vitamin D receptor gene polymorphisms on low-resistance training using exercise machines: the 'Power Rehabilitation' program. 査読国際誌

Shin-Ichiro Murakami, Takemi Otsuki, Megumi Maeda, Yoshie Miura, Seiko Morii, Kenji Kiyokane, Shin-Ichi Hayakawa, Atsushi Maeda, Takayo Imakawa, Shunpei Harada, Torataro Handa, Yasumitsu Nishimura, Shuko Murakami, Naoko Kumagai, Hiroaki Hayashi, Ying Chen, Shin-Ichiro Suemori, Yumiko Fukushima, Seikoh Nishida, Keisuke Fukushima

International journal of molecular medicine 23 ( 1 ) 81 - 8 2009年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

The enhancement and promotion of health is necessary to maintain the quality of life (QOL) of the aged population in developed nations such as Japan where the number of elderly has been increasing rapidly. For this purpose, low-resistance training using exercise machines ('Power Rehabilitation') has been established as a rehabilitation program. To investigate the individual factors which influence the effects of 'Power Rehabilitation', single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene and the ciliary neurotrophic factor (CNTF) gene were analyzed, and the relationship between SNP patterns and the effects of 'Power Rehabilitation' was evaluated. 'Power Rehabilitation' had an effect on the physiological functions involved in the activities of daily life (ADL) rather than muscle strength and size. In addition, certain SNP patterns showed better improvement of parameters associated with the effects of 'Power Rehabilitation' as analyzed by comparison between SNP patterns and factor analysis. Large scale analyses are required to ensure this tendency and to discover individual factors which may help to promote the health and QOL of the aged population.

DOI： 10.3892/ijmm_00000104

Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos 査読

Yasumitsu Nishimura, M. Maeda, N. Kumagai, H. Hayashi, Y. Miura, T. Otsuki

International Journal of Immunopathology and Pharmacology 22 ( 4 ) 879 - 888 2009年

掲載種別：研究論文（学術雑誌）

YT-CB5, which had been continuously cultured with chrysotile B (CB) asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by flow cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CBS also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2B4 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D, which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4. induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos. Copyright © by Biolife, s.a.s.

DOI： 10.1177/039463200902200403

珪肺症例末梢血CD4+25+分画における慢性活性化T細胞の混入とFas分子発現

林宏明, 前田恵, 村上周子, 西村泰光, 大槻剛巳, 藤本亘

山口医学 57 ( 4 ) 111 - 112 2008年8月

繊維・粒子状物質の生体影響とその周辺アスベストの免疫系への影響と腫瘍免疫減衰

大槻剛巳, 熊谷直子, 村上周子, 前田恵, 林宏明, 西村泰光

日本衛生学雑誌 63 ( 2 ) 236 - 237 2008年3月

Y2-4 アスベストの免疫影響の検討を踏まえたアスベスト曝露症例における免疫担当細胞の変化(胸膜疾患に対する診断の開発,要望演題2,第31回日本呼吸器内視鏡学会学術集会)

大槻剛巳, 前田恵, 三浦由恵, 村上周子, 林弘明, 熊谷直子, 西村泰光, 岸本卓巳, 中野孝司

気管支学 30 S114 2008年

珪肺症例におけるCD4+25+分画における慢性活性化Ｔ細胞、Fas分子発現の検討

林宏明, 前田恵, 村上周子, 西村泰光, 草加勝康, 大槻剛巳

日本臨床免疫学会総会抄録集 35 103 - 103 2007年

記述言語：日本語出版者・発行元：日本臨床免疫学会

珪肺症の合併症として自己免疫疾患の頻度が高いことは成書にも記されている。CD4+25+FoxP3+制御性Ｔ細胞（Treg）が，自己寛容維持に重要な役割を有することが知られてきた。CD4+25+ Treg の特異的発現機能遺伝子であるFoxP3 の発現が，健常人では，CD4+25+分画で高発現，CD4+25-分画で極めて低発現なのに比し，珪肺症例ではCD4+25+分画でも，CD4+25-分画と同程度に低発現なことを以前に報告した。活性化T細胞では発現しているが，CD4+25+Treg細胞では発現していないPD-1遺伝子の発現を，珪肺症例と健常人の末梢血単核球をCD4+25+分画とCD4+25-分画において検討した。結果，健常人ではどちらの分画でも非常に低発現であったが，珪肺症例では，CD4+25-分画でも健常人より高度に，CD4+25+分画では更に高度な発現が認められた。また、CD4+FoxP3+分画のFasの発現は健常人においてもCD4+FoxP3-分画に比し高発現の度合いが高かった。これらの結果より，珪肺症例のCD4+25+分画には珪酸曝露に伴う慢性活性化T細胞が侵入し，および珪肺症例の制御性T細胞では，Fas発現が高く容易にアポトーシスに至る可能性が示唆された。その結果FoxP3+ Tregを置換，CD4+25+分画の機能の減衰をもたらして自己寛容の破綻を招いている可能性が高いと考えられた。

DOI： 10.14906/jscisho.35.0.103.0

206 マンノース結合レクチンのスギ花粉症における役割(自然免疫, 第55回日本アレルギー学会秋季学術大会)

岡野光博, 前田恵, 村井綾, 藤原田鶴子, 木村吉伸, 西崎和則

アレルギー 54 ( 8 ) 1058 - 1058 2005年

291 遊離型糖鎖によるCryj1特異的T細胞応答の制御

岡野光博, 木村吉伸, 紀光助, 木村万里子, 菅田裕士, 道上佳洋, 前田恵, 松田史子, 西崎和則

アレルギー 51 ( 9 ) 979 - 979 2002年

293 遊離型糖鎖を用いたCryj1構成糖鎖のIgEエピトープ活性に関する検討

菅田裕士, 岡野光博, 木村吉伸, 紀光助, 木村万里子, 道上佳洋, 酒本真次, 前田恵, 西崎和則

アレルギー 51 ( 9 ) 980 - 980 2002年

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