| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Research Abstract |
Human mannose-binding-protein (MBP) is a serum lectin involving in the host defense via the complement activation. Thus, this complement activation is called lectin pathway. Recently, it was shown that the lectin pathway was intiated by a novel serine protease, termed MBP-associated serine protease (MASP), of which overall structure is similar to Cls or Clr. The present studies dealt with the identification of a serum protein possibly involving in the regulation of the MASP.
(1) We identified in serum a complex consisting of MBP,MASP and alpha2-macroglobulin.
(2) The binding order of these proteins was defined to be MBP-MASP-alpha2-macroglobulin by sandwich ELISA systems with two independent antibodies.
(3) The binding of MBP with MASP was Ca^<2+> dependent and reversible, while that between MASP and alpha2-macroglobulin was covalent and irreversible.
(4) The esterolytic activity of MASP was definitely inhibited by binding with alpha2-macroglobulin.
(5) There were two forms of MASP in serum, one binding with MBP and/or alpha2-macroglobulin and the other free from them. The levels of MASP in serum was much higher than those of MBP.
Ontogenic examination of MASP in serum disclosed that the level of MASP was high in infancy and declined with advance of ages of which tendency was quite similar to that of MBP.
Alfa2-macroglobulin is known to be a phylogenetically quite old protease-inhibitor with broad specificity. MBP is also known to be an old protein, the animal lectin. Thus, it is quite retinal that the lectin pathway, an old complement pathway, which remains and functions in the higher animals, is regulated by an old protease-inhibitor, alpha2-macroglobulin. The levels of MBP and MASP are higher in infancy and decline in advance of ages, indicating that the lectin pathway fully functions in the early ages when antibodies are not sufficiently emerged.
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