Suankratay C, Zhang X H, Zhang Y, Lint T F, Gewurz H
Department of Immunology/Microbiology, Rush Medical College, Chicago, IL 60612, USA.
J Immunol. 1998 Mar 15;160(6):3006-13.
Mannan-binding lectin (MBL) is a C1q-like molecule opsonic for several micro-organisms. MBL can activate C4, C2, and later acting complement components in the presence of serine proteases similar to but distinct from C1r and C1s via the lectin pathway of complement activation. We report here that mannan-coated MBL-sensitized erythrocytes are lysed via the lectin pathway in human serum-Mg-EGTA. The surprising occurrence of MBL-initiated lysis in the absence of calcium contrasts with the calcium requirement for C1q-initiated activation of C4 and C2. C2 is required, and lysis is significantly enhanced when indicator cells presensitized with C4 and then coated with mannan (EAC4-M) are used. The alternative pathway also is required, since lysis is lost when either factor D or factor B is removed and is restored upon reconstitution with the purified protein. Even though MBL is a C-type lectin, it is retained on mannan-coated erythrocytes in the absence of calcium. This contrasts with the absence of calcium-independent retention on mannan immobilized on polystyrene plates or beads, and helps explain the MBL-initiated hemolysis in Mg-EGTA. These investigations show that the alternative pathway as well as C4 and C2 of the classical pathway are required for complement-dependent hemolysis via the lectin pathway and provide a method for assay of lectin pathway-mediated complement activity in human serum that should be useful in unraveling the molecular interactions of this pathway.
甘露聚糖结合凝集素（MBL）是一种对多种微生物具有调理作用的C1q样分子。在类似于但不同于C1r和C1s的丝氨酸蛋白酶存在下，MBL可通过补体激活的凝集素途径激活C4、C2及后续起作用的补体成分。我们在此报告，在人血清-Mg-EGTA中，经甘露聚糖包被的MBL致敏红细胞通过凝集素途径被裂解。在没有钙的情况下MBL引发裂解这一令人惊讶的现象与C1q引发C4和C2激活对钙的需求形成对比。C2是必需的，当使用先用C4预致敏然后用甘露聚糖包被的指示细胞（EAC4-M）时，裂解会显著增强。替代途径也是必需的，因为当因子D或因子B被去除时裂解消失，而在用纯化蛋白重建后裂解恢复。尽管MBL是一种C型凝集素，但在没有钙的情况下它仍保留在经甘露聚糖包被的红细胞上。这与固定在聚苯乙烯板或珠子上的甘露聚糖不存在不依赖钙的保留情况形成对比，并有助于解释在Mg-EGTA中MBL引发的溶血现象。这些研究表明，替代途径以及经典途径的C4和C2对于通过凝集素途径的补体依赖性溶血是必需的，并提供了一种在人血清中测定凝集素途径介导的补体活性的方法，这对于阐明该途径的分子相互作用应该是有用的。
