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STUDIES ON MANNOSE-BINDING-PROTEIN (MBP) ; WITH SPECIAL REFERENCE TO COMPLEMENT ACTIVATION AND REGULATION,AND ITS DEPOSITION IN RENAL TISSUES

甘露糖结合蛋白（MBP）的研究；

基本信息

批准号：
07457176
负责人：
KOBAYASHI Kunihiko
金额：
$ 4.8万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

人甘露糖结合蛋白（MBP）是一种血清凝集素，通过激活补体参与宿主防御。因此，这种补体激活被称为凝集素途径。最近，研究表明凝集素途径是由一种新的丝氨酸蛋白酶启动的，称为MBP相关丝氨酸蛋白酶（MASP），其整体结构类似于Cls或Clr。本研究涉及可能参与MASP调节的血清蛋白的鉴定。(1)我们在血清中鉴定了由MBP、MASP和α 2-巨球蛋白组成的复合物。(2)通过具有两个独立抗体的夹心ELISA系统将这些蛋白质的结合顺序定义为MBP-MASP-α 2-巨球蛋白。(3)MBP与MASP的结合是Ca^<2+>依赖的、可逆的，而MASP与α 2-巨球蛋白的结合是共价的、不可逆的。(4)MASP的酯溶解活性通过与α 2-巨球蛋白结合而被明确抑制。(5)血清中有两种形式的MASP，一种与MBP和/或α 2-巨球蛋白结合，另一种不与它们结合。血清MASP水平明显高于MBP，MASP在婴儿期水平较高，随年龄增长而下降，其变化趋势与MBP相似。α 2-巨球蛋白是一种具有广泛特异性的蛋白酶抑制剂。MBP也被认为是一种古老的蛋白质，即动物凝集素。因此，很明显，凝集素途径（一种古老的补体途径）在高等动物中仍然存在并发挥作用，它受到一种古老的蛋白酶抑制剂α 2-巨球蛋白的调节。MBP和MASP的水平在婴儿期较高，随着年龄的增长而下降，表明凝集素途径在抗体未充分出现的早期充分发挥作用。