2001 Fiscal Year Final Research Report Summary
Studies on the functions of serine proteases and a novel-protein with low molecular size which are involved in the lectin complete pathway
| Project/Area Number |
11670328
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
MATSUSHITA Misao Fukushima Medical Univ. school of Medicine, Lecture, 医学部, 講師 (00165812)
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| Project Period (FY) |
1999 – 2000
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| Keywords | mannose-binding lectin / complement / lectin pathway / serine protease / MASP / sMAP / Ficolin |
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| Research Abstract |
Mannose-binding lectin (MBL) present in serum activates the complement system via the lectin pathway. Human MBL is associated with two types of Clr/Cls-like serine protease termed MASP and upon binding of MBL-MASP to carbohydrates, MASP cleaves C4, C2 and C3. MBL is also complexed with SMAP, a splicing variant of MASP-2. This study was aimed at elucidation of the activation mechanism of the lectin pathway in comparison with that of the classical pathway. Major achievements are as follows.
1) MASP-1 and MASP-2 were isolated from human serum and successfully separated MASP-1 was copurified with sMAP. MASP-1 activated C3 and C2, while MASP-2 activated C4 and C2. Cl inhibitor which is a serum inhibitor of Clr and Cls also inhibited both MASP-1 and MASP-2. 2) MBL forms oligomers with different molecular sizes. Among them, MBL trimer preparations contained MASP-1 and SMAP, while MBL oligomers with higher molecular sizes contained MASP-2 and newly identified MASP-3. 3) In human serum, MBL and Clq were found to be complexed with MASP, sMAP and Clr.Cls, respectively. Neither MBL-Clr, Cls complex nor Clq-MASP, SMAP complex was present in human serum. 4) Like MBL, ficolin/P35 which is a human serum lectin was associated with MASP- 1, MASP-2 and SMAP. The complex activated the complement system, implying that complement activation by ficolin/P35-MASP as well as MBL-MASP can be considered to be termed as the lectin pathway.
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