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戦略的基礎研究推進事業 平成７年度採択研究課題 研究終了報告  197-210
Fc受容体を介する生体防御システムの解析
高井 俊行

主な研究成果
(1) 高井グループ英文論文,著作発表(38件)
1. Snell, D., Pasquet, J-m., Becker, M., Lowell, C., Nieswandt, B., Ujike, A., Takai, T., Watson, S. The paired immunoglobulin-like receptor B has an inhibitory role in GPVI-dependent platelet activation. Submitted.
2. Kubo, S., Matsuoka, K., Taya, C., Kitamura, F., Takai, T., Yonekawa, H., Karasuyama, H. Drastic up-regulation of FcεRI on mast cells is induced by IgE binding through stabilization and accumulation of FcεRI on the cell surface. Submitted.
3. Kaifu, T., Nakahara, J., Mishima, K., Kaji, M., Inui, M., Ujike, A., Tan-Takeuchi, K., Iwasaki, K., Toyama-Sorimachi, N., Karasuyama, H., Fujiwara, M., Yokoyama, W.M., Asou, H., Takai, T. Dysmyelination in TYROBP-deficient mice implies primary CNS defect in Nasu-Hakola disease with dementia. Submitted.
4. Nakahara, J., Seiwa, C, Kaifu, T., Ujike, A., Inui, M., Tan-Takeuchi, K., Yagi, T., Aiso, S., Takai, T., Asou, H. Elucidating the mechanism of myelination: FcRγ-Fyn-MBP stream is critical for the CNS myelination. Submitted.
5. Yada, A., Clynes, R., Matsumura, K., Ebihara, S., Ono, M., Aiba, S., Inaba, K., Steinman, R.M., Ravetch, J.V., and Takai, T. Antigen targeting to Fcγ receptors on bone marrow-derived dendritic cells efficiently elicits humoral response and cytotoxic T lymphocytes in vivo. Submitted.
6. Schiller C, Moll T, Izui S, Takai T, Schmidt RE, Gessner JE. A requirement of phagocytic FcγRI and FcγRIII, but not FcγRII in the development of experimental autoimmune hemolytic anemia. Submitted.
7. Takai, T., and Ono, M. (2001) Activating and inhibitory nature of the murine paired Ig-like receptor (PIR) family. Immun. Rev. in press.
8. Max D. Cooper, Toshiyuki Takai, Jeffrey V. Ravetch (Ed.): Activating and Inhibitory Immunoglobulin-Like Receptors. Springer-Verlag Tokyo, 2001.
9. Takai, T., Nakamura, A. Autoimmune arthritis and Goodpasture’s syndrome induced in Fcg receptor-deficient mice. In: (M.D. Cooper, T. Takai, J.V. Ravetch eds) Activating and Inhibitory Immunoglobulin-Like Receptors. pp. 189-198, Springer-Verlag Tokyo, 2001.
10. Ono, M., Takai, T. Function of gp49A in mast cell activation. In: (M.D. Cooper, T. Takai, J.V. Ravetch eds)Activating and Inhibitory Immunoglobulin-Like Receptors. pp. 99-106, Springer-Verlag Tokyo, 2001.
11. Yoneto, T., Waki, S., Takai, T., Tagawa, Y., Iwakura, Y., Mizuguchi, J., Nariuchi, H., and Yoshimoto, T. (2001) A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. J. Immunol. 166: 6236-6241.
12. Kaji, K., Takeshita, S., Miyake, K., Takai, T., and Kudo, A. (2001) Functional association of CD9 molecule with FcγIII receptor in macrophages. J. Immunol. 166: 3256-3265.
13. Yuasa, T., Ono, M., Watanabe, T., and Takai, T. (2001) Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction. J. Exp. Med. 193: 563-572.
14. Lee, K.H., Ono, M., Inui, M., Yuasa, T., and Takai, T. (2000) Stimulatory function of gp49A, a murine Ig-like receptor, in RBL-2H3 cells. J. Immunol. 165:4970-4977.
15. Onah DN, Uchiyama F, Nagakui Y, Ono M, Takai T, Nawa Y. (2000) Mucosal defence against gastrointestinal nematodes: Responses of mucosal mast cells and mouse mast cell protease 1 during primary Strongyloides venezuelensis infection in FcRγ-knockout mice. Infect. Immun. 68: 4968-4971.
16. Wakayama, H., Hasegawa, Y., Kawabe, T., Hara, T., Matsuo, S., Mizuno, M., Takai,T., Kikutani, H., Shimokata, K. (2000) Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice. Eur. J. Immunol. 30:1182-1190.
17. Schiller, C., Janssen-Graalfs, I., Baumann, U., Schwerter-Strumpf, K., Izui, S., Takai, T., Schmidt, R.E., and Gessner, J.E. (2000) Mouse FcγRII is a negative regulator of FcγRIII in IgG immune complex triggered inflammation but not in autoantibody induced hemolysis. Eur. J. Immunol. 30:481-490.
18. Nakamura, A., Yuasa, T., Ujike, A., Ono, M., Nukiwa, T., Ravetch, J.V., Takai, T. (2000) Fcγ receptor IIB-deficient mice develop Goodpasture’s syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease. J. Exp. Med. 191:899-906.
19. Cortegano, I., del Pozo, V., Cardaba, B., Arrieta, I., Gallardo, S., Rojo, M., Aceituno, E., Takai, T., Verbeek, S., Palomino, P., Liu, F.-T., and Lahoz, C. (2000) Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene: Implication of the promoter sequence IL-5REIII. Glycobiol. 10:237-242.
20. Ujike, A., Ishikawa, Y., Ono, M., Yuasa, T., Yoshino, T., Fukumoto, M., Ravetch, J. V., and Takai, T. (1999) Modulation of IgE-mediated systemic anaphylaxis by low affinity Fc receptors for IgG. J. Exp. Med. 189:1573-1579.
21. Yuasa, T., Kubo, S., Yoshino, T., Ujike, A., Matsumura, K., Ono, M., Ravetch, J.V., and Takai, T. (1999) Deletion of FcγRIIB renders H-2b mice susceptible to collagen-induced arthritis. J. Exp. Med. 189: 187-194.
22. Clynes, R., Maizes, J.S., Guinamard, R., Ono, M., Takai, T., and Ravetch, J.V. (1999) Modulation of immune complex induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J. Exp. Med. 189: 179-186.
23. Ono, M., Yuasa, T., Ra, C., and Takai, T. (1999) Stimulatory function of paired immunoglobulin-like receptor-A (PIR-A) in mast cell line by associating with subunits common to Fc receptors. J. Biol. Chem. 274: 30288-30296.
24. Yamashita, Y., Ono, M., and Takai, T. (1998) Inhibitory and stimulatory functions of the paired immunoglobulin-like receptor (PIR) family in RBL-2H3 cells. J. Immunol. 161: 4042-4047.
25. Suzuki Y, Shirato I, Okumura K, Ravetch JV, Takai T, Tomino Y, Ra C. (1998) Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis. Kidney Int. 54: 1166-1174.
26. Maeda, A., Kurosaki, M., Ono, M., Takai, T., and Kurosaki, T. (1998) Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal. J. Exp. Med. 187: 1355-1360.
27. Watanabe, N., Nomura, T., Takai, T., Chiba, T., Honjo, T., and Tsubata, T. (1998) Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces rapid apoptosis of normal spleen B cells. Scand. J. Immunol. 47: 541-547.
28. Yamashita, Y., Fukuta, D., Tsuji, A., Nagabukuro, A., Matsuda, Y., Nishikawa, Y., Ohyama, Y., Ohmori, H., Ono, M., and Takai, T. (1998) Genomic structures and chromosomal location of p91, a novel murine regulatory receptor family J. Biochem. 123, 358-368.
29. Kuroiwa, A., Yamashita, Y., Inui, M., Yuasa, T., Ono, M., Nagabukuro, A., Matsuda, Y., and Takai, T. (1998) Association of tyrosine phosphatases SHP-1 and SHP-2, and inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene. J. Biol. Chem. 273: 1070-1074.
30. Takai, T., Ono, M., Ujike, A., Yuasa, T. (1998) Regulation of murine hypersensitive responses by Fc receptors. Allergol. Intern. 47: 75-83.
31. Takai T, Ravetch, JV: Fc receptor genetics and the manipulation of genes in the study of FcR biology. In: Immunoglobulin Receptors and their Physiological and Pathological Roles in Immunity, Eds J. G. J. van de Winkel and P. Mark Hogarth, Kluwer Academic Publishers, Netherland, pp. 37-48, 1998.
32. Takai T, Yamashita Y, Nishikawa Y, Fukuta D, Ohyama Y, Inui M, Hikida M, Ohmori H, Ono M: p91, a novel murine KIR-like molecule expressed on macrophages and mast cells. In: Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. (ed. Yakura H), pp. 359-360, Springer-Verlag, Tokyo, 1997.
33. Hikida, M., Mori, M., Kawabata, T., Takai, T., and Ohmori, H. (1997) Characterization of B cells expressing recombination activating genes in germinal centers of immunized mouse lymph nodes. J. Immunol. 158: 2509-2512.
34. Hayami, K., Fukuta, D., Nishikawa, Y., Yamashita, Y., Inui, M., Ohyama, Y., Hikida, M., Ohmori, H., and Takai, T. (1997) Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. J. Biol. Chem. 272: 7320-7327.
35. Hikida, M., Mori, M., Takai, T., Tomochika, K., Hamatani, K., and Ohmori, H. (1996) Reexpression of RAG-1 and RAG-2 Genes in Activated Mature Murine B cells. Science 274, 2092-2094.
36. Hikida, M., Takai, T., and Ohmori, H. (1996) Requirements of a costimulus for IL-4-induced IgE class switching in murine B cells activated via antigen receptors: Effectiveness of 8-mercaptoguanosine. J. Immunol. 156: 2730-2736.
37. Takai, T., Ono, M., Hikida, M., Ohmori, H., and Ravetch, J. V. (1996) Augmented humoral and anaphylactic responses in FcγRII-deficient mice. Nature 379: 346-349.
38. Takai, T. (1996) Multiple loss of effector cell functions in FcRγ-deficient mice. Intern. Rev. Immunol. 13: 369-381.
(2) 高井グループ和文総説·解説·著作発表(58件)
1. 氏家あづさ, 中村晃, 小野栄夫, 高井俊行: Fcγレセプターとアレルギー反応. アレルギー科 11: 268-274(2001).
2. 高井俊行: Fcレセプター. 免疫学·分子生物学キーワード辞典, 医学書院, 東京(2001)
3. 中村晃, 小野栄夫, 貫和敏博, 高井俊行: Fcγ受容体遺伝子欠損マウス. 最新医学 特集:慢性関節リウマチ-遺伝子異常とその修復. 56: 871-876(2001)
4. 中村晃, 小野栄夫, 貫和敏博, 高井俊行: Fcγレセプター欠損マウス.最新医学 印刷中. (2001).
5. 小林哲夫, 高井俊行, 吉江弘正: Fcγレセプター遺伝子型による歯周炎感受性診断.先端医療シリーズ·歯科医学2:「歯周病-新しい治療を求めて」(岡田,石川,村山他編)先端医療技術研究所(2000)
6. 高井俊行(編): 特集「Fcレセプターの基礎と臨床」最新医学 最新医学社, 東京(2000)
7. 小野栄夫, 海老原伸, 秋山健一, 貫和敏博, 高井俊行: Fc受容体と腫瘍免疫 最新医学 55: 2316-2321(2000).
8. 中村晃, 小野栄夫, 貫和敏博, 高井俊行: Fc受容体と自己免疫疾患モデルマウス 最新医学 55: 2310-2315(2000)
9. 高井俊行: 「Fcレセプターの基礎と臨床」序論およびアプローチ 最新医学 55: 2271-2272, 2273-2279 最新医学社(2000)
10. 高井俊行: 「Fcレセプター」BioScience用語ライブラリー 羊土社 p.103-104(2000)
11. 小野栄夫, 竹田和彦, 高井俊行: 抑制性シグナル伝達分子. 医学のあゆみ 192: 1049-1055(2000)
12. 高井俊行: FcRとILRをつなぐもの 文部省科学研究費特定領域研究「免疫病の分子機構とその修復」ニュースレター8 pp19-21(2000).
13. 矢田あゆみ, 高井俊行: FcγRI(CD64) 臨床免疫臨時増刊 印刷中.
14. 小野栄夫, 高井俊行: 免疫グロブリンFc受容体を介した免疫抑制機構. 化学と生物 38: 154-160(2000)
15. 中村晃, 氏家あづさ, 石川陽子, 小野栄夫, 高井俊行: マスト細胞の活性化とFcγレセプター 臨床免疫, 33(2): 149-153(2000)
16. 高井俊行, 氏家あづさ, 石川陽子: アナフィラキシーとFcレセプター欠損マウス. 呼吸, 19: 534-539(2000).
17. 高井俊行, 小野栄夫, 乾匡範, 石川陽子: Igファミリーレセプターによる細胞活性化とDAP12. 臨床免疫 33: 130-136(2000)
18. 小野栄夫, 高井俊行: 免疫系における受容体を介した抑制シグナル. アレルギー科 印刷中.
19. 小野栄夫, 高井俊行: FcγRIIBを介するB細胞の負の制御 臨床免疫 印刷中
20. 竹田和彦, 高井俊行: NKレセプターp70/p140 臨床免疫臨時増刊 印刷中
21. 小野栄夫, 小林哲夫, 石川陽子, 吉江弘正, 高井俊行: FcγレセプターIII(CD16)臨床免疫臨時増刊 32: 652-656(1999)
22. 高井俊行: 抗炎症薬の開発への新規自己免疫疾患モデル動物利用の可能性を探る(第20回日本炎症学会ワークショップ報告). Medical Academy News. 729号 p.7 薬事日報社 東京 1999年.
23. 氏家あづさ, 小野栄夫, 高井俊行: FcγレセプターIIB 臨床免疫 32: 647-651(1999).
24. 高井俊行, 小野栄夫, 久場川博三: PIRによる細胞活性化調節 Ann Rev 免疫 2000 320-327(1999).
25. 高井俊行, 小野栄夫: 活性化と抑制の両者を制御するPIR 免疫1999-2000 36: 46-54(1999).
26. 小野栄夫, 小林哲夫, 石川陽子, 吉江弘正, 高井俊行: FcγレセプターIII 臨床免疫 32: 652-656(1999).
27. 氏家あづさ, 石川陽子, 小野栄夫, 高井俊行: FcγRIIBによるアレルギーの制御. アレルギー科 7: 472-477(1999).
28. 高井俊行, 小野栄夫: FcγレセプターIIBを介するB細胞の負の制御機構. 臨床免疫 32: 320-324(1999).
29. 高井俊行: Fcレセプターとアナフィラキシー. アレルギー. 48: 1291-1295(1999).
30. 高井俊行, 小野栄夫, 湯浅貴恵, 氏家あづさ: Fcレセプターおよびキラー·レセプターによる免疫制御機構. 第22回阿蘇シンポジウム記録集「免疫学のニューフロンティア」(渡邊武, 西村泰治, 柳雄介編)南山堂 東京(1999)pp67-78.
31. 高井俊行, 小野栄夫, 乾匡範: NK活性とキラー抑制レセプター. 臨床免疫 31: 40-46(1999).
32. 山下由美, 高井俊行, 大森斉: Killer-cell inhibitory receptor (KIR)によるNK細胞の制御. Annunal Review 免疫 192-202(1998).
33. 高井俊行: Fcレセプター分子群による免疫制御と疾患. 東北医学雑誌 110: 189-192 (1998)
34. 高井俊行: アレルギーとFcgレセプター: 免疫·Immunology Frontier, 8, 305-309 (1998).
35. 高井俊行: Fc受容体の機能. 組織培養工学 24: 332-335(1998).
36. 高井俊行: Fcレセプター分子群による免疫制御. 加齢医学研究所雑誌 49: 107-118 (1998).
37. 高井俊行: ゼロのシステムとDAP12 JSI Newsletter 6: 17(1998)
38. 高井俊行, 小野栄夫, 氏家あづさ: Fcγ受容体 現代医療 30, 290-293(1998).
39. 高井俊行(分担執筆): Fcレセプター·ノックアウトマウス: 「Annual Review 免疫 1998」 菊地浩吉, 矢田純一, 奥村康 編, 中外医学社 pp.312-320 (1998).
40. 高井俊行(分担執筆): Fcレセプターγノックアウトマウス: 「分子アレルギー学」徳久剛史, 羅智靖 編, pp.327-331, メディカルレビュー社, 東京(1998).
41. 高井俊行, 小野栄夫: アレルギーとFcレセプター Molecular Medicine 34: 1464-1476 (1997)
42. 高井俊行: Fcレセプターによる免疫制御機構: 生化学 69, 394-409(1997).
43. 高井俊行: ノックアウトマウスによる免疫研究: 実験医学, 15, 50-54 (1997).
44. 高井俊行: FcRノックアウトマウスを用いたアレルギー発症機構の解析 アレルギー科 4: 471-477 (1997).
45. 高井俊行(分担執筆): 炎症の分子生物学: 「標準免疫学」谷口克, 宮坂昌之編, 医学書院, 東京 pp.390-401 (1997).
46. 高井俊行(分担執筆): アレルギーとFcレセプター: 実験医学別冊「免疫研究の最前線’97-’98」笹月, 北村, 中山, 山本 編, 羊土社 東京 pp. 172-179(1997).
47. 高井俊行, 小野栄夫, 山下由美: Fcレセプターを介するB細胞の抑制: 臨床免疫, 29: 550-555 (1997).
48. 高井俊行: FcγRノックアウトマウスを用いたアレルギー発症機構の解析: アレルギーの臨床 17, 422-427(1997).
49. 高井俊行, 小野栄夫: FcγRIIノックアウトマウスにおけるマスト細胞の異常活性化: 臨床免疫, 29, 227-234 (1997).
50. 高井俊行(分担執筆): Fc receptor(FcR)ノックアウトマウス「ノックアウトマウス·データブック」pp. 169-170, 中山書店, 東京, (1997).
51. 高井俊行: Fcレセプターと抗体産生制御: 臨床免疫, 29: 898-904 (1997).
52. 高井俊行: Fcレセプター欠損マウス: Molecular Medicine, 34: 44-54 (1997).
53. 高井俊行: Fcレセプターの新展開: 感染·炎症·免疫 27: 80-89 (1997).
54. 高井俊行: FcRとKIRとの境目 JSI Newsletter 5: 5 (1997)
55. 高井俊行: Fcレセプター·ノックアウトマウス: 免疫·Immunology Frontier, 6, 153-158 (1996).
56. 高井俊行(分担執筆): Fcγレセプターによる免疫制御: 「免疫’96-97」, pp.145-153 中山書店, 東京(1996).
57. 高井俊行: FcγRとアレルギー(とくにFcγRII): アレルギー科, 2, 136-143 (1996).
58. 高井俊行: IgGのFcレセプターとアレルギー: 臨床免疫, 28, 1062-1068 (1996).
(3) 高井グループ·海外学会発表
1) 招待、口頭講演 (9件)
2) ポスター発表 (7件)
1. T. Takai: The 3rd World Congress on Inflammation (Tokyo International Forum, Tokyo, 11/16-20/97) Symposium: Signal Transduction in Immunocytes: NEGATIVE REGULATION OF IMMUNE RESPONSES BY FCγRIIB
2. T. Yuasa, et al. The 3rd World Congress on Inflammation (Tokyo International Forum, Tokyo, 11/16-20/97) Poster presentation: AUGMENTED INFLAMMATORY RESPONSES IN FCγRIIB-DEFICIENT MICE
3. Yamashita T et al. The 3rd World Congress on Inflammation (Tokyo International Forum, Tokyo, 11/16-20/97) Poster presentation: CHARACTERIZATION OF p91, A NOVEL MURINE KIR-LIKE MOLECULE EXPRESSED ON MACROPHAGES
4. Takai T et al. The 13th TMIN International Symposium (Arcadia Ichigaya, Tokyo, 10/15-17, 1997) Organized by Dr. Hidetaka Yakura. Theme: Kinases and Phosphatases in Lymphocytes and Neuronal Signaling. Poster and Oral presentation: Characterization of A Novel Murine KIR-like Molecule, p91
5. Pishel J et al. MITOGENICITY OF ANTI-TCR/CD3 MABS ATTRIBUTABLE TO INEFFECTIVE CROSS-LINKING OF LOW-AFFINITY FCγ RECEPTORS.
13th European Immunology Meeting (22-25 June ’97 Amsterdam)
6. Ono M et al. INHIBITORY AND STIMULATORY FUNCTIONS OF THE PAIRED IMMUNOGLOBULIN-LIKE RECEPTOR (PIR) FAMILY IN MAST CELL. International Congress on Immunology. November, 1998 New Delhi, India.
7. Yuasa et al. DELETION OF FcγRIIB RENDERS H-2b MICE SUSCEPTIBLE TO COLLAGEN-INDUCED ARTHRITIS. Experimental Biology ’99, April 17-21, 1999, Washington DC.
8. Ujike A et al. MODULATION OF IgE-MEDIATED SYSTEMIC ANAPHYLAXIS BY MURINE LOW AFFINITY Fc RECEPTORS FOR IgG. Experimental Biology ’99, April 17-21, 1999, Washington DC.
9. Ono M et al. INHIBITORY AND STIMULATORY FUNCTIONS OF THE PAIRED IMMUNOGLOBULIN-LIKE RECEPTOR (PIR) FAMILY IN MAST CELLS. Experimental Biology ’99, April 17-21, 1999, Washington DC.
10. Yuasa et al. DELETION OF FcγRIIB RENDERS H-2b MICE SUSCEPTIBLE TO COLLAGEN-INDUCED ARTHRITIS. Mediators of Inflammation 8: suppl 1, 1999, pp. S52-S53 (The 4th International Congress on Inflammation; June 26-29, Paris, 1999).
11. Nakamura A, Yuasa T, Ujike A, Ono M, Nukiwa T, Ravetch JV, Takai T. Goodpasture’s syndrome induced in FcγRIIB-deficient mice. FIMSA2000 Taipei, Thailand January 23-27, 2000.
12. Takai T: Negative regulation of allergic response by Fcg receptor. The Recent Topics in Immunodermatology. The first forum of the Japanese Society of Immunodermatology, Tokyo, March 1997. invited
13. Takai T: Negative regulation of immune responses by FcγRIIB. The Third World Congress on Inflammation, Tokyo, November 1997. invited
14.Takai T: Analysis of hypersensitive responses in Fc receptor-deficient mice. International Complement Workshop: Complement receptors, Fc receptors and Immune reactions. (Organized by Taro Kinoshita, 6/23/99 Tokyo) invited
15. T. Takai, A. Nakamura, T. Yuasa, A. Ujike, M. Ono, T. Nukiwa and J.V. Ravetch: Fcγ Receptor IIB-Deficient Mice Develop Goodpasture’s Syndrome Upon Immunization With Type IV Collagen. Workshop on Novel Autoimmune Animal Model. May 13. Immunology 2000 Seattle USA May 12-16.
16. Takai T: generation and analysis of PIR-B-deficient mice. The CREST International Symposium on Immunoglobulin-Like Receptors. Sendai International Center 9/20/2000
(4) 高井グループ特許出願(国内8件,PCT出願中)
1. 高井俊行, 山下由美, 小野栄夫: (1997)脱リン酸化酵素を阻害する新規ペプチド. 日本国内特許(岡山大学経由)整理番号: PJ012924 受付番号: 39729400023 出願番号: 特願平09-362285号 公開番号: 特開平11-169184号 公開日1999.06.29
2. 濱田宗雄, 岡本全泰, 中田勝彦, 高井俊行(1999)アナフィラキシー抑制物質のスクリーニング方法. 整理番号: A031P37 出願番号: 特願平11-124788
3. 中村晃, 貫和敏博, 高井俊行: Goodpasture症候群モデルマウス(1999)特願平11-180600
4. 矢田あゆみ, 松村公男, 小野栄夫, 相場節也, 高井俊行: 免疫応答誘導樹状細胞の調製方法(1999)平成11年8月24日出願. 整理番号A031P45. 出願番号: 特願平11-237597
5. 名和行文, 小野栄夫, 高井俊行: 寄生虫感染排除に関する発明. 出願中.
6. 中村晃, 貫和敏博, 高井俊行: リウマチ関節炎高発症モデルマウス. 特願平11-373366
7. 湯浅貴恵, 小野栄夫, 渡邊武, 高井俊行: III型アレルギー炎症モデル動物. 特願2000-253984
8. 高井俊行, 阿相皓晃, 藤原道弘: オリゴデンドロサイト発達障害モデル非ヒト動物.
(5) 高井グループその他特記事項
自己免疫疾患モデル動物に関する特許は(株)オリエンタルバイオサービスに実施許諾され,現在,一般利用に向けて頒布の準備を進めている.
(6) 羅グループ英文論文発表 (53件)
1. Hano, T., Ra, C., Nonoyama, K., Suzuki, K., Yata, J. and Nakahata, T. Induction of the high-affinity IgE receptor (FcεRI) on human mast cells by IL-4. Int. Immunol., 8: 1367-1373, 1996.
2. Vugt, M.J., Heijnen, I.A.F.M., Capel, P.J.A., Park, S.Y., Ra, C., Saito, T., Verbeek, J.S., and Winkel, J.G.J. FcRγ chain is essential for both stable expression and function of human FcγRI (CD64) in vivo. Blood, 87: 3593-3599, 1996.
3. Yamaguchi, M., Hirai, K., Ohta, K., Suzuki, K., Kitani, S., Takaishi, T., Ito. K., Ra, C., and Morita, Y. Nonreleasing basophils convert to releasing basophils by culturing with interleukin-3. J. Aller. Clin. Immunol., 97: 1279-1287, 1996.
4. Pawankar, R.U., Okuda, M., Suzuki, K., Okumura, K., and Ra, C. Phenotypic and molecular characteristics of nasal γδ T cells in allergic and infectious rhinitis. Amer. J. Resp. Crit. Care Med., 152: 1655-1665, 1996.
5. Naito, K., Hirama, M., Okumura, K. and Ra, C. Recombinant soluble form of the human high affinity receptor for IgE inhibits anaphylactic shock in mice. J. Aller. Clin. Immunol., 97: 773-780, 1996.
6. Shibaki, A., Ohkawara, A., Shimada, S., Ra, C., Aiba, S., and Cooper, K.D. Expression, but lack of calsium mobilization by high-affinity IgE Fcε receptor I on human epidermal and dermal Langerhans cells. Exp. Dermatol., 5: 272-278, 1996.
7. Pawankar, R., and Ra, C. Heterogeneiy of mast cells and T cells in the nalsal mucosa. J. Allergy Clin. Immunol., 98: 5248-5262, 1997.
8. Matsuda, H., Watanabe, N., Geba, G.P., Sperl, J., Tsudzuki, M., Hiroi, J., Matsumoto, M., Ushio, H., Saito, S., Askenase, P.W., and Ra, C. Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int. Immunol., 9: 461-466, 1997.
9. Pawankar, R., Okuda, M., Yssel H., Okumura, K., and Ra C. Nasal mast cells in perennial allergic thinitics exhibit increased expression of the FcεRI, CD40L, IL-4 and can induce IgE synthesis in B cells. J. Clin. Invest., 99: 1492-1499, 1997.
10. Sagara, H., Matsuda, H. Yagita, H., Fukuda, T., Okumura, K., Makino, S. and Ra, C. A monoclonal antibody against very late activation antigen-4 (VLA-4) inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma. Int. Arch. Allergy Immunol., 112: 287-294, 1997.
11. Toru, H., Kinashi, T., Ra, C., Nonoyama, S., Yata, J. and Nakahata, T. Interleukin-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules. Blood, 89: 3296-3302, 1997.
12. Wada, N., Okumura, K., and Ra, C. Evaluation of FcεRI-bindable human IgE with an enzyme-linked immunosorbent assay using a recombinant soluble form of the human FcεRIα ectodomain. Allergol. Int., 46: 173-180, 1997.
13. Honda, Z., Suzuki, T., Hirose, N., Aihara, M., Shimizu, T., Nada, S., Okada, M., Ra, C., Morita, Y., and Ito, K. Roles of C-terminal Src kinase in the initiation and the termination of the high affinity IgE receptor-mediated signaling. J. Biol. Chem., 272: 25753-25760, 1997.
14. Arase, N., Arase, H., Park, S.Y., Ohno, H., Ra, C., and Saito, T. Association with FcRγ is essential for activation signal through NKR-P1 (CD161) in NK cells and NK1.1+T cells. J. Exp. Med., 186: 1957-1963, 1997.
15. Yanagihara, Y., Kajiwara, K., Basaki, Y., Ikizawa, K., Ebisawa, M., Ra, C., Tachimoto, H., and Saito, H. Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation. Clin. Exp. Immunol., 111: 136-143, 1998.
16. Suzuki, K., Hirose, T., Matsuda, H., Hasegawa, S., Okumura, K., and Ra, C. The Fc receptor (FcR)γ subunit is essential for IgE-binding activity of cell-surface expressed chimeric receptor molecules constructed from human high-affinity IgE receptor (FcεRI)α and FcRγ subunits. Molecular Immunology, 35: 259-270, 1998.
17. Pawanakar, R., and Ra, C. IgE-FcεRI-Mast cell axis in the Allergic Cycle. Clin. Exp. Allergy, 28: 6-14, 1998.
18. Park, S.Y., Ueda, S., Ohno, H., Tanaka, M., Shiratori, T., Yamazaki, T., Hamano, Y., Karasawa, A., Sato, S., Ledermann, B., Kondo, Y., Okumura, K., Ra, C., and Saito, T. Resistance of Fc receptor-deficient mice to fatal glomerulonephritis. J. Clin. Invest., 102: 1229-1238, 1998.
19. Toru, H., Pawankar, R., Ra, C., Ishida, H., Nonoyama, S., Yata, J., and Nakahata, T. Human mast cells produce IL-13 by high affinity IgE receptor cross-linkig : Enhanced IL-13 production by IL-4-primed human mast cells. J. Aller. Clin. Immunol., 102: 491-502, 1998.
20. Suzuki, Y., Shirato, I., Okumura, K., Ravetch, J.V., Takai, T., Tomino, Y., and Ra, C. FcR and angiotensin II-dependent pathways distinctively contribute to the pathogonesis of anti-GBM antibody induced glomerulonephritis : Study in FcRγ and FcγRII deficient mice. Kidney International, 54: 1166-1174, 1998.
21. Hasegawa, S., Pawankar, R., Suzuki, K., Nakahata, T., Furukawa, S., Okumura, K., and Ra, C. Functional expression of the high affinity receptor for IgE (FcεRI) in human platelets and megakaryocytes. Blood, 93: 2543-2551, 1999.
22. Hayashi, S., Okumura, K., and Ra, C. Mouse langerhans cells do not express the high affinity receptor for IgE. Arch. Dermatol. Res., 291: 241-243, 1999.
23. Hiraoka, S., Furumoto, Y., Koseki, H., Takagaki, Y., Taniguchi, M., Okumura, K., and Ra, C. The Fc receptor β subunit is required for full activation of mast cells through Fc receptor engagement. Int. Immunol., 11: 199-207, 1999.
24. Goitsuka, R., Hayashi, N., Nagase, M., Sasaki, N., Ra, C., Tsujimoto, H., and Hasegawa, A. Molecular cloning of cDNAs encoding canine high-affinity IgE receptor α, γ and γ-chain. Immunogenetics,49: 580-582, 1999.
25. Yamaguchi, M., Sayama, K., Yano, K., Lantz, C.S., Noben-Trauth, N., Ra, C., Costa, J.J., and Galli, J. IgE enhances Fcε receptor I expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cells: Synergistic effect of IL-4 and IgE on human mast cell Fcε receptor I expression and mediator release. J. Immunol., 162: 5455-5465, 1999.
26. Nishiyama, C., Yokota, T., Okumura, K., and Ra, C. The transcription factors Elf-1 and GATA-1 bind to cell specific-enhancer elements of human Fc epsilon alpha chain gene. J. Immunol., 163:623-630, 1999.
27. Ono, M., Yuasa, T. ,Ra, C., Takai, T. Stimulatory Function of Paired Immunoglobulin-like Receptor-A in Mast Cell Line by Associating with Subunits Common to Fc Receptos. J. Biol. Chem., 274: 30288-30296, 1999.
28. Suzuki, Y., Ra, C., Saito, K., Horikoshi, S., Hasegawa, S., Tsuge, T., Okumura, K., Tomino, Y. Expression and physical associstion of Fcα receptor and Fc receptor γchain in human mesangial cells. Nephrol. Dial. Transplant., 14: 1117-1123, 1999.
29. Atsuta, R., Akiyama, K., Shirasawa, T., Okumura, K., Fukuchi, Y., Ra, C. Atopic asthma is dominant in elderly onset asthmatics : possibility for an alteration of mast cell function by aging through Fc receptor expression. Int. Arch. Allergy Immunol., 120: 76-81, 1999.
30. Matsumoto, S., Wada, N., Ohno, S., Okumura, K. ,Ra, C. Evaluation of FcεRI-binding serum IgE in patients with ocular allergic diseases. Allergol. Int., 48: 183-187, 1999.
31. Hasegawa, S., Pawankar, R., Suzuki, K., Nakahata, T., Furukawa, S., Okumura, K., and Ra, C. Functional expression of the high affinity receptor for IgE (FcεRI) in human platelets and megakaryocytes. Blood, 93: 2543-2551, 1999.
32. Matsuoka, K., Taya, C., Kubo, S., Toyama Sorimachi, N., Kitamura, F., Ra, C., Yonekawa, H., Karasuyama, H. Establishment of antigenn-specific IgE transgenic mice to study pathological and immunobiological roles of IgE in vivo. Int. Immunol. 11: 987-994, 1999.
33. Wada, T., Toma, T., Shimura, S., Kudo, M., Kasahara, Y., Koizumi, S., Ra, C., Seki, H., Yachie, A. Age-Dependent Increase of IgE-Binding and FcεRI Expreesion on Circulating Basophils in Children. Pediatr. Res., 46: 603-607, 1999.
34. Honda, Z., Suzuki, T., Kono, H., Okada, M., Yamamoto, T., Ra, C., Morita, Y., Yamamoto, K. Sequential requirements of N-terminal palmitoylation site and SH2 domain of Src family kinases in the initiation and progression of FcεRI signaling. Molecular and Cellular Biol., 20: 1759-1771, 2000.
35. Hayashi, S., Suto, H., Wada, N., Ogawa, H., Okumura, K., Ra, C . Detection of anti-IgE and anti-FcεRIαchain auto-antibodies In patients with atopic dermatitis. Allergol. Int. 49: 47-54,2000.
36. Yanagida, M., Irikura, M., Suto, H., Yagi, S., Ogawa, H. and Ra, C. Kinetic Analysis of the Interaction between Recombinant Human FcεRI α and Serum IgEs from Allergic Patients. Clin. Immunol. 95-3: 190-196, 2000.
37. Furumoto, Y., Hiraoka, S., Kawamoto, K., Masaki, S., Kitamura, T., Okumura, K and Ra, C. Polymorphisms in FcεRI β Chain Do Not Affect IgE-Mediated Mast Cell Activation. Biochem. Bioph. Res. Co. 273-2: 765-771,2000.
38. Shimokawa, T., Okumura, K and Ra, C. DNA Induces Apoptosis in Electroporated Human Promonocytic Cell Line U937. Biochem. Bioph. Res. Co. 270-1. 94-99, 2000.
39. Takai, T., Yuuki, T., Iwamoto-Yasue, N., Okumura, K and Ra, C. Epitope analysis and primary structures of variable regions of anti-human FcεRI monoclonal antibodies and expression of the chimeric antibodies fused with human constant regions. Biosci., Biotech. and Biochem. 64: 1856-1867, 2000.
40. Takai, T., Yuuki, T and Ra, C. Inhibition of IgE-dependent histamine release from human peripheral blood basophils by humanized Fab fragments that recognize the membrane proximal domain of the human FcεRI α chain. Int. Arch. Allergy and Immunol. 123: 305-318, 2000.
41. Nishiyama, C., Takahashi, K., Nishiyama, M. ,Okumura, K. Ra, C., Ohtaka,Y and Yokota,T. Splice isoforms of transcription factor Elf-1 affecting its regulatory function in transcription. Biosci.Biotech. and Biochem. 64-12: 2601-2607, 2000.
42. Shimokawa, T., suge, T., Okumura, K and Ra, C. Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcαR,CD89). Immunogenetics. 51: 945-954, 2000.
43. Asai K., Fujimoto K., Harazaki M., Kusunoki T., Korematsu S., Ide C., Ra C., Hosoi S. Distinct aggregation of β-and γ-chains of the high-affinity IgE receptor on crosslinking, J. Histochem. Cytochem. 48: 1705-1715, 2000.
44. Takai, T., Okumura, K and Ra, C. Direct expression of the extracellular portion of human FcεRI α chain in Esherichia coli. Biosci, Biotech., and Biochem. 65: 79-85, 2001.
45. Takahashi, K., Nishiyama, C. ,Okumura, K., Ra, C.,Ohtaka, Y and Yokota, T. Molecular cloning of rat USF2 and characterization of splicing variants. Biosci. Biotech. and Biochem. 65: 56-62, 2001.
46. Takai T., Okumura K., Ra C., Yokota T., Okumura Y., Expressopn of Humanized fab Fragments That Recognize The IgE-Binding Domain OF Human FcεRIα in COS and CHO Cells. J. Biochem. 129: 5-12, 2001.
47. Iida. M,. Matsumoto. K,. Tomita. H,. Nakajima. T,. Akasawa. A,. Yuyama. N,. Yoshida. N.L,. Matsui. K,. Nakada. A,. Sugita. Y,. Shimizu. Y,. Wakahara. Y, Nakao. T,. Fujii. Y, .Ra. C, and Saito. H. Selective down-regulation of high-affinity IgE receptor (FcεRI)α-chain messenger RNA among transcriptome in code blood-derived versus adult peripheral blood-derived cultured human mast cells. Blood. 97: 1016-1022. 2001.
48. Tsuge, T., Shimokawa, T., Horikoshi, S., Tomino,Y. and Ra, C. Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy. Hum Genet 108: 128-133, 2001.
49. Takahashi, K., Nishiyama, C. ,Okumura, K., Ra, C., Ohtaka, Y and Yokota, T. A complex composed of USF1 and USF2 activates the human FcεRI α chain expression via CAGCTG element in the first intron. Eur.J.Immunol. (In press), 2001.
50. Aioi, A., Tonogaito, H., Suto, H., Hamada, K., Ra, C., Ogawa, H., Maibach, H. and Matsuda, H. Defective skin barrier function in NC/Nga mice. Brit. J. Dermato. (In press), 2001.
51. Takahashi, K., Yuuki, T., Takai, T., Ra, C., Yokota, T., Okumura, Y. Production of humanized Fab fragment against human high affinity IgE receptor in Pichia pastoris. Biosci., Biotech, and Biochem. (In press), 2001.
52. Gounne, A.S., Lamkhioued, B.L., Koussih, L., Ra, C., Renzi, P.M. and Hamid, Q. Human neutrophils express the high-affinity receptor for immunoglobulin E(FcεRI): role in asthma. FASEB J. 15:(inpress), 2001.
53. Yamaguchi, M., Hirai, K., Komiya, A., Miyamasu, M., Furumoto, Y .,Ra, C. and Yamamoto, K. Regulation of mouse mast cell surface FcεRI expression by dexamethasone. Int.Immunol, 13-7: (inpress), 2001.
(7) 羅グループ口頭発表:省略
(8) 中田グループ:主な研究成果
特許1件
口頭発表(国内3件、海外1件)
濱田宗雄、岡本全泰、中田勝彦、高井俊行, アレルギー性結膜炎におけるFcγRIIBによる制御機構, 免疫·アレルギー週間連合学会, ポートピアホテル(兵庫県神戸市), 1998年12月3日
濱田宗雄、岡本全泰、中田勝彦、高井俊行, アレルギー性結膜炎とFcγレセプター, 加齢研/CRESTシンポジウム「Fcレセプターの基礎と臨床」, 宮城県仙台市東北大学艮陵会館記念ホール, 1999年2月24日
濱田宗雄、岡本全泰、中田勝彦、高井俊行, Regulatory role of Fcγ receptor IIB in conjunctival anaphylaxis in mice, The Association for Research in Vision and Ophthalmology, Fort Lauderdale,Florida, USA, 1999年5月12日
濱田宗雄、宮地俊、中田勝彦、高井俊行, FcγRIIBノックアウトマウスにおけるアレルギー性結膜炎, 日本眼薬理学会, 京都市北文化会館, 2000年9月8日