1994 Fiscal Year Final Research Report Summary
Mechanism of comploment activation by MBP
| Project/Area Number |
05670307
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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 |
Immunology
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| Research Institution | Fukushima Medical College |
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Principal Investigator |
MATSUSHITA Misao Fukushima Medical college Dept. of Medicine, Assistant Professor, 医学部, 講師 (00165812)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Tetsuo Fukushima Medical college, Dept. of Medicine Assistant Professor, 医学部, 助手 (00235368)
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| Project Period (FY) |
1993 – 1994
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| Keywords | mannose-binding protein / complement / MASP / serine protease |
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| Research Abstract |
Mannose-binding protein (MBP) is a serum lectin and plays an important role in the innate immunity. After binding to pathogens possessing carbohydrates such as mannose, MBP activates the complement system, resulting in the killing them. In serum, MBP complexes with a C1s-like serine protease termed MASP (MBP-associated serine protease). Upon binding of MBP to its ligands, MASP cleaves C4 and C2. In our research project, we investigated the structure and function of MASP to clarify the mechanisms of the complement activation mediated by MBP.We have obtained the following results.
1.The unactivated MASP has been isolated from human serum. It has a molecular size of approximately 93 kDa with a single polypeptide. Although it has no C4-cleaving activity, it acquires this activity when MBP binds to mannan.
2._<alpha2>-macroglobulin binds to and inhibits MASP.
3.MASP has the proteolytic capacity to cleave C3 with subsequent activation of the alternative complement pathway, a capacity which C1s lacks.
4.The Gly-52--Asp allelic form of MBP found in the patients with MBP deficiency fails to bind MASP.
5.From the results of cDNA analysis, MASP has been found to have structural similarities to C1r/C1s. For instance, the six domains found in C1r/C1s are conserved in MASP.
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