Rimoldi M T, Tartanian A, Joiner K A
Laboratory of Parasitic Diseases, National Institute of Allergy, Bethesda, Maryland 20892.
Exp Parasitol. 1989 Feb;68(2):160-7. doi: 10.1016/0014-4894(89)90093-3.
Infective and vertebrate stages of Trypanosoma cruzi are resistant to lysis by the alternative pathway of complement. To further elucidate the mechanism of complement evasion and to study how some immune sera render the infective stage sensitive to lysis, we compared the interaction of complement components C3 and C9 with the surface of complement susceptible, vector stage epimastigotes and vertebrate stage trypomastigotes of T. cruzi. Our studies showed that, upon incubation in human serum, complement resistant tissue culture trypomastigotes (TCT) bound five- to eightfold less C3 or C9 than complement sensitive epimastigotes (Epi). C3 bound to Epi is mainly in the hemolytically active C3b form, while TCT bear predominantly the hemolytically inactive iC3b fragment, which cannot participate in C5 convertase formation or lead to deposition of the lytic C5b-9 complex. Three- to sixfold more C3 and two- to threefold more C9 were deposited on TCT when lytic rabbit immune IgG with broad specificity was used to sensitize the parasites, and nearly one-half of bound C3 was present as C3b. In contrast, a comparison of three different sources of IgG from immune human serum showed a less clear correlation between the titer or specificity of anti-T. cruzi antibody, enhancement of C3 or C9 deposition, change in the form of bound C3, or killing. These results show that lytic rabbit IgG for T. cruzi changes the form and amount of bound complement components in anticipated fashion, but that human immune IgG does not give predictable changes in the extent or form of C3 or C9 deposition.
克氏锥虫的感染性阶段和脊椎动物阶段对补体替代途径介导的裂解具有抗性。为了进一步阐明补体逃避机制,并研究某些免疫血清如何使感染性阶段对裂解敏感,我们比较了补体成分C3和C9与克氏锥虫补体敏感的媒介阶段无鞭毛体和脊椎动物阶段锥鞭毛体表面的相互作用。我们的研究表明,在人血清中孵育后,补体抗性的组织培养锥鞭毛体(TCT)结合的C3或C9比补体敏感的无鞭毛体(Epi)少五至八倍。结合到Epi上的C3主要是具有溶血活性的C3b形式,而TCT主要携带无溶血活性的iC3b片段,该片段不能参与C5转化酶的形成或导致溶细胞性C5b-9复合物的沉积。当使用具有广泛特异性的溶细胞性兔免疫IgG使寄生虫致敏时,TCT上沉积的C3增加三至六倍,C9增加二至三倍,并且结合的C3中近一半以C3b形式存在。相比之下,对来自免疫人血清的三种不同来源的IgG进行比较,结果显示抗克氏锥虫抗体的效价或特异性、C3或C9沉积的增强、结合C3形式的变化或杀伤之间的相关性不太明显。这些结果表明,针对克氏锥虫的溶细胞性兔IgG以预期的方式改变了结合的补体成分的形式和数量,但人免疫IgG在C3或C9沉积的程度或形式上并未产生可预测的变化。