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Molecular Structure and Function of a Novel Immunoinhibitory Protein Institute of Immunological Science

Research Project

Project/Area Number 63480164
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionHokkaido University

Principal Investigator

SUGIMURA Kazuhisa  Hokkaido University, Associate Prof., 免疫科学研究所・化学部門, 助教授 (80127240)

Co-Investigator(Kenkyū-buntansha) SAIKI Ikuo  Institute of Immunological Science Hokkaido University, Assistant Prof., 化学部門, 助手 (80133776)
AZUMA Ichiro  Institute of Immunological Science Hokkaido University, Professor, 化学部門, 教授 (50028411)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsLymphocyte Blastogenesis Inhibitory Factor / Mycoplasma Arginine / Arginine Deiminase Gene / Arginine Metabolism / Autoimmune Disease / MRL Mice / Hyperactive B Lymphocytes / LBIF / LBIF遺伝子 / 細胞内情報伝達機構 / サイトカイン / 細胞増殖 / 細胞周期 / IL-2レセプター / U937 / 増殖抑制 / 免疫制御
Research Abstract

In 1987, we identified a cell growth inhibitor, Iymphocyte blastogenesis inhibitory factor (LBIF) in the culture supernatant of a human histiocytic lymphoma, U937. In this study, we have attempted to clarify the molecular structure and function of LBIF. Results are summarized below.
1. It has been shown that LBIF is an arginine deiminase (EC 3.5.3.6) originated from Mycoplasma arginine, infecting U937 cells.
2. The nucleotide sequence of full-length cDNA clone encoding LBIF has been determined.
In a next series of functional analyses of LBIF, we have examined the effects of LBIF on the antibody production of autoimmune MRL mice in vitro.
3. It was demonstrated that the IgG antibody production was not inhibited by LBIF in spite of strong inhibition of IgA and IgM antibody production. These results were confirmed by culturing B cells in arginine-free medium supplemented with varying doses of urea cycle metabolities.
4. Thus, we demonstrated that gamma-committed B lymphocytes (B gamma) of MRL … More mice selectively expressed the highly elevated Lーarginine syntyhesis while mu or alpha-committed B lymphocyted showed the normal level.
5. Normal murine lymphocytes are hardly able to utilize Lーcitrulline to grow and numal lymphocytes are not able to use Lーcitrulline at all.
Important implication of our findings are as follows and this abnormality sufficiently explain four important questions of systemic autoimmune disease, such as, (1), predominant propagation of gamma^+ cells, (2), predominant IgG production, (3), disease progression with aging and (4), drastic effects of dietary restriction on the disease manifestation.
Autoimmune diseases so far, tend to be considered on the basis of clonal selection (tolerance) or cytokine-responsiveness. This study strongly suggests that systemic autoimmune diseases should be reevaluated as metabolic disorders occurred in lymphocytes, whereas organ-specific autoimmune diseases may belong to immunological disorders with the abnormality of clonal selection. Thus, this study presents a novel perspective on the molecular mechanism of systemic autoimmune disease. Less

Report

(3 results)
  • 1990 Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 杉村 和久: "Fast protein liquid chromatography of lymphocyte blastogenesis inhibitory factor produced by the human macrophageーlike cell line U937." J.Chromatography. 440. 131-140 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "A lymphocyte blastogenesis inhibitory factor(LBIF)arrests mitogenーstimulated T lymphocytes at early Gl phase with no influence on interleukin 2 production and interleukin 2 recptor light chain expression." Eur.J.Immunol.19. 1357-1364 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "Tumor growth inhibitory activity of a lymphocyte blastogenesis inhibitory factor(LBIF)." Caner Res.50. 345-349 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "Abnormal behavior of γーcommitted B lymphocytes probed by a lymphocyte blastogensis inhibitiory factor,LBIF in autoimmune MRL mice." Eur. J. Immunol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "Identification and purification of arginine deiminase originated from Mycoplasma arginini." Infection and Immunity. 58. (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 大野 剛: "Cloning and nucleotide sequence of the gene encoding arginine deiminase originated from Mycoplasma arginini." 投稿中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "Eleveted argininosuccinate synthetase activity in abult T leukemia cell lines." Leukemia Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "Inherited hyperactivation of Lーargininc synthesis in γ^+ lymphocytes of systemic autoimmune MRL mice."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 竹田 浩治: "リンパ球増殖制御と免疫抑制" Minophaqen Medical Review. 33. 201-213 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 上田 豊: "リンパ球の発生と分化" 病態生理. 8. 446-459 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久: "免疫不応答性の分子機序" Medical Immunolgy. 17. 591-597 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 土生 芳樹: "抑制性サイトカイン,Annual Review免疫1989" 中外医学社, 295 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村 和久(日本語訳): "最新医科学の焦点,リンホカインの分子生物学(D.Male編,In Focus,Lymphokine,A.S Hamblin,IRL press)" 南江堂,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Tsukahara, K., Ueda, Y., Takeda, K., Habu, Y., and I. Azuma.: "Fast Protein Liquid Chromatography of Lymphocyte Blastogenesis Inhibitory Factor Produced by the Human Macrophage-Like Cell Line U937." J. Chromatography. 440. 131-140 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Ueda, Y., Takeda, K., Fukuda, S., Tsukahara, K., Habu, Y., Fujiwara, H., and I. Azuma.: "A Lymphocyte Blastogenesis Inhibitory Factor (LBIF) Arrests Mitogenstimulated T Lymphocytes at Early G1 Phase With no Influence on Interleukin 2 Production and Interleukin 2 Receptor Light Chain Expression." Eur. J. Immunol.19. 1357-1364 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Ohno, T., Fukuda, S., Wade, Y., Kimura, T., and I. Azuma.: "Tumor Growth Inhibitory Activity of a Lymphocyte Blastogenesis Inhibitory Factor (LBIF)." Cancer Res.50. 345-349 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Ohno, T., Wada, Y., Ued, Y., Kimura, T., and I. Azuma.: "A Lymphocyte Blastogenesis Inhibitory Factor (LBIF) Reversibly Arrests a Human Melanoma Cell Line, A375 at Gl and G2 Phases of Cell-Cycle." Exp. Cell. Res.188. 272-278 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Wada, Y., Kimura, T., Ohno, T., Kobayashi, S., and I. Azuma.: "Abnormal Behavior of Gamma-Committed B Lymphocytes Probed by a Lymphocyte Blastogenesis Inhibitory Factor, LBIF in Autoimmune MRL Mice." Eur. J. Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Fukuda, S., Wada, Y., Taniai, M., Suzuki, M., Kimura, T., Ohno, T., Yamamoto, K., and I. Azuma.: "Identification and Purification of Arginine Deiminase Originated from Mycoplasma Arginine" Infection and Immunity. 58. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohno, T., Ando, O., Sugimura, K., Taniai, M., Suzuki, M., Fukuda, S., Nagase, Y., Yamanoto, K., and I. Azuma.: "Cloning and Nucleotide Sequence of the Gene Encoding Arginine Deiminase Originated from Mycoplasma Arginine."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Kimura, T., Arakawa, H., Ohno, T., Wada, Y., Kimura, Y., Saheki, T., and I. Azuma.: "Elevated Argininosuccinate Synthetase Activity in Adult T Leukemia Cell Lines." Leukemia Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sugimura, K., Wada, Y., Kimura, T., Ohno, T., Kobayashi, S., and I. Azuma.: "Inherited Hyperactivation of L-arginine Synthesis in Gamma^+B Lymphocytes of Systemic Autoimmune MRL Mice."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 杉村和久: "A lymphocyte blastogenesis inhibitory factor(LBIF)arrests mitogen-stimulated T lymphocytes at early Gl phase with no influence on interleukin 2 production and interleukin 2 receptor light chain expression." Eur.J.Immunol.19. 1357-1364 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 杉村和久: "Tumor growth inhibitory activity of a lymphocyte blastogenesis inhibitory factor(LBIF)." Cancer Res.50. 345-349 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 杉村和久: "A lymphocyte blastogenesis inhibitory factor(LBIF)reversibly arrests a human melanoma cell line,A375 at Gl and G2 phases of cell-cycle." Exptl.Cell Res.(1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 杉村和久: "Abnormal behavior of γ-committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor,LBIF in autoimmune MRL mice."

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Sugimura,et al.: Jounal of Chromatography. 440. 131-140 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 竹田浩治: "Minophagen Medical Review;リンパ球増殖制御と免疫抑制" ミノファーゲン製薬, 201-213 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 土生芳樹: "Annual Review 免疫 1989;抑制性サイトカイン" 中外医学社, 100-108 (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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