Meri S, Morgan B P, Davies A, Daniels R H, Olavesen M G, Waldmann H, Lachmann P J
Molecular Immunopathology Unit, Medical Research Council, Cambridge, U.K.
Immunology. 1990 Sep;71(1):1-9.
Human cells are relatively resistant to lysis by the homologous complement system. Here we describe the mechanism of action of a recently discovered and widely distributed 18,000-20,000 molecular weight (MW) membrane glycoprotein (CD59), which appears to act as a major protective element against complement-mediated lysis (hence called protectin). When incorporated into heterologous erythrocyte membranes, protectin efficiently prevented cell lysis by human serum. Neutralization with antibody of the naturally occurring protectin on human erythrocytes or on nucleated K562 cells increased their susceptibility to lysis by homologous complement. During complement activation, protectin became incorporated into the membrane attack complex (MAC). By interacting with newly exposed regions in the C5b-8 complex and in aggregating C9 it limited the number of C9 molecules associating with the C5b-8 complex to a C8:C9 ratio of 1:1.5 instead of a normal average of 1:3.5. The results demonstrate directly that protectin is a powerful inhibitor of complement cytolysis and acts by inhibiting the C5b-8 catalysed insertion of C9 into the lipid bilayer.
人类细胞对同源补体系统介导的细胞溶解具有相对抗性。在此，我们描述了一种最近发现且广泛分布的分子量为18,000 - 20,000的膜糖蛋白（CD59）的作用机制，它似乎是抵抗补体介导的细胞溶解的主要保护因子（因此称为保护素）。当整合到异源红细胞膜中时，保护素能有效防止人血清介导的细胞溶解。用抗体中和人红细胞或有核K562细胞上天然存在的保护素，会增加它们对同源补体介导的细胞溶解的敏感性。在补体激活过程中，保护素会整合到膜攻击复合物（MAC）中。通过与C5b - 8复合物中新暴露的区域相互作用以及聚集C9，它将与C5b - 8复合物结合的C9分子数量限制为C8:C9比例为1:1.5，而不是正常平均的1:3.5。结果直接表明保护素是补体细胞溶解的强力抑制剂，其作用机制是抑制C5b - 8催化C9插入脂质双层。
