1996 Fiscal Year Final Research Report Summary
A NOVEL LECTIN-DEPENDENT ACTIVATION PATHWAY OF COMPLEMENT
| Project/Area Number |
06454223
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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 |
Immunology
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| Research Institution | FUKUSHIMA MEDICAL COLLEGE |
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Principal Investigator |
FUJITA Teizo FUKUSHIMA MEDICAL COLLEGE,BIOCHEMISTRY,PROFESSOR, 医学部, 教授 (20134223)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Takashi FUKUSHIMA MEDICAL COLLEGE,BIOCHEMISTRY,ASSISTANT, 医学部, 助手 (80254001)
MATSUSHITA Misao FUKUSHIMA MEDICAL COLLEGE,BIOCHEMISTRY,ASSISTANT PROFESSOR, 医学部, 講師 (00165812)
ENDO Yuichi FUKUSHIMA MEDICAL COLLEGE,BIOCHEMISTRY,ASSOCIATE PROFESSOR, 医学部, 助教授 (20117427)
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| Project Period (FY) |
1994 – 1996
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| Keywords | MBP (MBL) / MASP (MASP1, MASP2) / lectin pathway molecular development / 分子進化 |
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| Research Abstract |
Serum mannose-binding protein (MBP) is a C-type lectin capable of activating the complement system (the lectin pathway). A serine protease designated MASP (MBP-associated serine protease) is involved in the activation by MBP,exerting C4-and C2-activating capacity when bound to MBP on its ligands.
1)A novel serine protease, MASP has ability to cleave C3, subsequently activating the altemative pathway. We analyzed MASP genomic clones and found that the light chain is encoded by six exons, whereas that of C1r/C1s have been reported to be single exon.
2)We investigated reconstitution of recombinant MBPs and MASP for exhibiting complement activation. Wild type rMBP was found to be able to be associated with MASP,resulting in complement activation, whereas rMBP_D in which glycine is substituted with asparatic acid in the fifth collagen repeat is unable to activate complement when incubated with MASP.These results indicate that lack of complement-activating capacity of rMBP_D might be due to in
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ability of association with MASP.
3)We found that several human glioma cell lines can bind to MBP and to activate the lectin pathway.
4)alpha2-macroglobulin were able to bind to MBP-MASP complex and to inhibit the MASP activity. Also we established the assay system of serum concentration of MASP using an enzyme linked immunosorbent assay (ELISA) found 6 mug/ml in normal human serum.
5)To elucidate the origin and evolution of MASP,we cloned six MASP cDNA from five vertebrates going mammal to cyclostome. An alignment of the amino acid sequences revealed the presence of two different lineages of the MASP gene.
6)We isolated the lectin-protease complex and C3 from body fluids of Japanese Ascidian, Halocynthia roretzi (Hoya). The purified lectin binds specifically to zymosan, components of yeast cell wall through glucose residue but not to mannose. A serine protease bound to this lectin has a similar property of the MASP and it cleaves ascidian C3. We would like to propose that the lectin pathway is an origin of the complement system consisting of the recognition molecule, serine protease activating C3 and C3 which functions as an opsonin. Thus, the lectin pathway plays an important role in innate immunity. Less
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