A novel lectin-dependent activation pathway of complement
Grant-in-Aid for International Scientific Research.
|Research Institution||Fukushima Medical College|
FUJITA Teizo Department of Biochemistry, Fukushima Medical College, 医学部, 教授 (20134223)
リード ケネス オックスフォード大学, MRC, 教授
エゼユビッツ アラン ハーバード大学, 医学部, 教授
水落 次男 東海大学, 工学部, 教授 (90133149)
小林 邦彦 北海道大学, 医学部, 教授 (60091451)
松下 操 福島県立医科大学, 医学部, 講師 (00165812)
MIZUOCHI Tsuguo Department of Applied Chemistry, Tokai University
EZEKOWITZ Alan Department of Pediatrics, Harverd Medical School
MATSUSHITA Misao Department of Biochemistry, Fukushima Medical College
KOBYASHI Kunihiko Department of Pediatrics, Hokkaido University School of Medicine
REID Kenneth b m MRC.University of Oxford
|Project Fiscal Year
1995 – 1995
Completed(Fiscal Year 1995)
|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥2,000,000 (Direct Cost : ¥2,000,000)
|Keywords||complement / lectin pathway / MBP / MASP / C1 / 補体 / レクチン経路 / CI|
Serum mannose-binding protein (MBP) is a C-type lectin capable of activating the complement system (the lectin pathway). A novel 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.We investigated reconstitution of recombinant MBPs and MASP for exhibiting complement activation. Wild type recombinant MBP (MBP_G) was found to be able to be associated with MASP,resulting in complement activation, whereas recombinant mutated MBP (MBP_D) in which glycine (G) is substituted with asparatic acid (D) in the fifth collagen repeat and responsible for the complement-dependent opsonic defect is unable to activate complement when incubated with MASP.These results indicate that lack of complement-activating capacity of MBP_D might be due to inability of association with MASP (Biochem.J., 1995).
2.To clarify the mechanisms by which C1r/C1s is substitute for MASP in the activation of the lectin pathway, we measured the affinity constant of C1r/C1s or C1q and MBP using a Biacore apparatus. The results indicate that affinity constants of the four possible mixtures are very similar. Since only MBP-MASP and C1q-C1r/C1s complexes were present in serum, the other factors would influence the interaction of MBP and C1r/C1s.
3.To evaluate the role of the MASP in various diseases, we established sandwich ELISA using several monoclonal antibodies. The mean value of normal human is about 6mug/ml. Estimation of MASP in various diseases is currently under investigation.
Research Output (10results)