APOPTOSIS AND COMPLEMENT-STUDIES ON THE MECHANISM OF COMPKEMENT ACTIVATION AND THE BIOLOGICAL SIGNIFICANCE
| Project/Area Number |
08457601
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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.of Pharm.Sci., Prof., 薬学部, 教授 (70029958)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Yusuke Hokkaido Univ.Fac.of Pharm.Sci., Assostant., 薬学部, 教務職員 (10250466)
NISHIMURA Hitoshi Hokkaido Univ.Fac.of Pharm.Sci., Assostant., 薬学部, 助手 (80241347)
TAKAHASHI Kazuhiko Hokkaido Univ.Fac.of Pharm.Sci., As., Prof., 薬学部, 助教授 (10113581)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | COMPLEMENT / APOPTOSIS / PHAGOCYTOSIS / OPSONIN / IMMUNOLOGY / MACROPHAGE / アポトシス / ガン細胞 / 生体防御 |
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| Research Abstract |
We investigated the mechanism of autologous complement activation by apoptotic cells and biological significance of complement activation in the clearance of apoptotic cells by macrophages.
1. Activator of the autologous complement pathway in apoptotic cells. Complement activation does not occur on homologous live cells.We observed the activation of the autologous complement pathway by human apoptotic cells, suggesting the appearance of a novel complement activator on apoptotic cells.To characterize the novel activator, Jurkat Y cell line was allowed to spoptosis and its cell proteins were subjected to SDS-PAGE and subsequently treated with human serum as a source of complement.Complemnt activation occurred on a 50 KDa protein, which was become deposited with C3b, suggesting the presence of 50 KDa molecule capable of activating autologous complement.The same molecule was detected in the membrane fraction of live cells. Based on these data, we proposed that the 50 KDa activator protein i
… More
s located in the membrane fraction of live cells and become exposed to cell surface upon apoptosis.Studies on the isolation of the novel complement activator are now in progress.
2. The effect of complement activation upon phagocytosis of qpoptotic cells by macrophages.We found that serum-treated apoptotic cells were labeled with ic3b, which is known as an opsonin. This suggested that ic3b on apoptotic cells might interact with CR3 of macrophages and promote the phagocytosis of apoptotic cells.The ic3b-coated apoptotic cells were found to be phagocytosed much more quickly than ic3b-noncoated cells by macrophages.The phagocytosis of ic6b-coated apoptotic cells by macrophages was found to be inhibited by anti-ic6b antibodies and anti-CR3, indicating that ic3b on apoptotic cells should interact with CR3 on macrophages and promote the clearance of apoptotic cells by phagocytes.Thus, complement is not only a host defense system but also a physiological system to remove unnecessary cells, such as apoptotic cells. Less
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Report
(3 results)
Research Products
(14 results)
