| Project/Area Number |
03671118
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Osaka Medical College |
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Principal Investigator |
HATANAKA Michiyo Osaka Medical College, Clinical Pathol., Assistant Prof, 医学部, 助手 (50218484)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Akira Osaka Medical College, Clinical Pathol., Prof., 医学部, 教授 (00028581)
稲井 真弥 大阪医科大学, 医学部, 教授 (90131317)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Complement / C9 / Monoclonal antibodies / DTT / GPI-anchor / PNH / DAF / MACIF(CD59) / モノクロ-ナル抗体 / 合成ペプチド / DTT / ジスルフィド結合 |
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| Research Abstract |
The complement system consist of more than 20 serum proteins and play an important role in host defense. Complement component C9 exerts at the final step of complement cascade by inserting into membranes which contain preformed C9 acceptor, C5b-8. C9 proceeds drastic conformational changes upon interaction with C5b-8 complex. Although the entire primary structure has already been demonstrated, the structual and function relationship is not fully ubderstood. In this research, we intended to clarify the mechanisms of C9 activation by using monoclonal antibodies to C9 and also with chemical modification reagent, DTT. It has been demonstrated that
1. Two seperate epoitipes of C9 are involved in C5b-8 binding.
2. Functional domains of C9 are supported by disulfide bridges.
3. Different and distinct domains of disulfide bridges are implicated in binding to C5b-8, hemolytic activity, and self-polymerization of C9.
Complement functions are targeted only on non-self membranes, and activation does not occur on self membranes. Complement regulating proteins (DAF, MACIF, MCP, CR1) have now been demonstrated to play the crucial roles in self- and non-self determination. We have assesed the function of DAF and MACIF by inccorporating the isolated proteins to PNH erythrocytes which deffect these proteins.
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