| Project/Area Number |
04454527
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
NAGASAWA Shigeharu Hokkaido Univ. Fac.Pharm.Sci.Professor, 薬学部, 教授 (70029958)
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| 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)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| 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)
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| Keywords | Complement / Immunology / Anaphylatoxin / Host defense / Endothelial cells / Receptor |
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| 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.
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