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Studies on molecular constitution and effector functions of complement system

Research Project

Project/Area Number 04454527
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHokkaido University

Principal Investigator

NAGASAWA Shigeharu  Hokkaido Univ. Fac.Pharm.Sci.Professor, 薬学部, 教授 (70029958)

Co-Investigator(Kenkyū-buntansha) YAMASHITA Toshiyuki  Hokkaido Univ. Fac.Pharm.Sci.Research assistant, 薬学部, 助手 (90192400)
TAKAHASHI Kazuhiko  Hokkaido Univ. Fac.Pharm.Sci.Assistant professor, 薬学部, 助教授 (10113581)
ARIGA Hiroyoshi  Hokkaido Univ. Fac.Pharm.Sci.Professor, 薬学部, 教授 (20143505)
NAGASAWA Shigeharu  Hokkaido Univ. Fac.Pharm.Sci.Professor (70029958)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1993: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1992: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsComplement / Immunology / Anaphylatoxin / Host defense / Endothelial cells / Receptor
Research Abstract

1.A conformational change in C4 : Using monoclonal antibody against a neoantigen in C4, we have determined a specific hydrophobic domain in C4, which becomes exposed from interior portion to the surface upon activation of C4 by C1s.
2.Structure and functions of regulatory factors of complement system : We have compared the regulatory effects of MCP, DAF, and MCP-DAF hybrid molecule against human complement by expressing the factors on Chinese hamster ovary cells. Hybrid molecule exerted additive protective effect against the alternative pathway of complement but was less potent in the classical pathway than DAF alone.
3.Histamine-induced expression of DAF on human umbilical vein endothelial cells (HUVEC) : DAF expression on HUVEC was found to be enhanced about 2 fold with 10 mM histamine through H_1 receptor. These results suggest that histamine, which is released from mast cells and basophils by C5a anaphylatoxin, increases the complement defense ability of endothelial cells by increaseing their levels of DAF expression.
4.Biological functions and receptors of anaphylatoxins, C3a and C4a. We have revealed the presence of two types of C3a receptor on guinea pig macrophages and found that C3a receptor-mediated cellular responses are down-regulated by C4a. These results suggest that contrary to general assumption, C4a receptor is functionally different from C3a receptor.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Maeda,S.: "Identification of a surface structure in the fourth component of human complement,C4,which becomes hidden upon activation by C1s." Biochem.J.289. 503-508 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami,Y.: "Characterization of C3a anaphylatoxin receptor on guinea-pig macrophages." Immunology. 79. 633-638 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami,Y.: "Cellular responses guinea-pig macrophages to C4a:Inhibition of C3a-induced O2┣D1-┫D1┫D1┣D22┣D1-┫D1 generation " Immunol.Lett.36. 301-304 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuruta,T.: "Novel function of C4a anaphylatoxin:Release from monocytes of protein which inhibits monocyte chemotaxis." Am.J.Pathol.142. 1848-1857 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kojima,A.: "Membrane cofactor protein(CD46)protects cells predominantly from alternative complement pathway-mediated C3 fragment deposition and cytolysis." J.Immunol.151. 1519-1527 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuji,S.: "Decay-accelerating factor on human umbilical vein endothelial cells.Its histamine-induced expression and spontaneous rapid shedding from the cell surface." J.Immunol.153. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 長澤滋治: "補体系-プロテアーゼとそのインヒビター:生理的意義および病態との関連" メジカルビュー, 9 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Maeda, S.& Nagasawa, S.: "Identification of a surface structure in the fourth component of human complement, C4, which becomes hidden upon activation by C1s." Biochem. J.289. 503 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami, Y., Imamichi, T., & Nagasawa, S.: "Characterization of C3a anaphylatoxin receptor on guinea pig macrophages." Immunology 7. 9. 633 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Murakami, Y., Yamamoto, T., Imamichi, T., & Nagasawa, S.: "Cellular responses of guinea pig macrophages to C4a ; inhibition of C3a-induced O_2 generation by C4a." Immunol. Left. 36. 301 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuruta, T., Yamamoto, T., Matsubara, S., Nagasawa, S., Tanase, S., Tanaka, J., Takagi, K.& Kambara, T.: "Novel function of C4a anaphylatoxin : release from monocytes of protein which inhibits monocyte chemotaxis." Am.J.Pathol. 142. 1848 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kojima, A., Iwata, K., Seya, T., Matsumoto, M., Ariga, H., & Nagasawa, S.: "Membrane cofactor protein (CD46) protects cells predominantly from alternative complement pathway-mediated C3-fragment deposition and cytolysis." J.Immunol. 151. 1519 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuji, S., Kaji, K., & Nagasawa, S.: "Decay accelerating factor on human umbilical vein endothelial cells. Its histamine-induced expression and spontaneous rapid shedding from the cell sruface." J.Immunol. 153.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Iwata, K., Seya, T., Ariga, H., Nagasawa, S.: "Expression of a hybrid complement regulatory protein, membrane cofactor protein decay accelerating factor on CHO cells. Comparison of its regulatory effect with those of decay accelerating factor and membrane cofactor protein." J.Immunol. 153 in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kojima,A.: "Membrane cofactor protein(CD46)protects cells predominantly from alternative complement pathway-mediated C3 fragment deposition and cytolysis." J.Immunol.151. 1519-1527 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsuji,S.: "Decay-accelerating factor on human umbilical vein endothelial cells.Its histamine-induced expression and spontaneous rapid shedding from the cell surface." J.Immunol.153(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwata,K.: "Expression of a hybrid complement regulatory protein,membrane cofactor protein decay-accelerating factor on CHO cells." J.Immunol.153(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 長澤滋治: "補体系-プロテアーゼとそのインヒビター:生理的意義および病態との関連" メジカルビュー, 9 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Maeda,S.: "Identification of a surface structure in the fourth component of human complement,C4,which becomes hidden upon activation by C1s." Biochem.J.289. 503-508 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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