EVASION OF ALTERNATIVE COMPLEMENT PATHWAY BY TRYPANOSOMA-CRUZI RESULTS FROM INEFFICIENT BINDING OF FACTOR-B
EVASION OF ALTERNATIVE COMPLEMENT PATHWAY BY TRYPANOSOMA-CRUZI RESULTS FROM INEFFICIENT BINDING OF FACTOR-B
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DOI：
10.1073/pnas.83.17.6593
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发表时间：
1986-09-01
影响因子：
11.1
通讯作者：
HAMMER, C
中科院分区：
文献类型：
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作者：
JOINER, K;SHER, A;HAMMER, C
在昆虫载体分化为对哺乳动物宿主具有感染性的阶段期间，克氏锥虫通过补体替代途径对裂解产生抗性。为了阐明补体逃避的机制，我们研究了克氏锥虫非感染性上鞭毛体和感染性培养物衍生的后循环锥鞭毛体阶段（CMT）表面补体激活的控制。研究发现，上鞭毛体上补体成分 C3 的主要形式是 C3b，而 CMT 上的大部分 C3 是以溶血性失活片段 iC3b 的形式存在，它不能参与 C5 转化酶的形成或导致溶解性 C5b-9 复合物的沉积。我们的结果还表明，在上鞭毛体阶段和 CMT 中，C3 通过共价酯键与不同分子量的表面分子结合。纯化补体成分的结合研究表明，CMT 不支持替代途径 C3 转化酶的有效形成。 寄生虫表面上的 C3b 无法结合放大成分 B 因子，而不是显示出与对照成分 H 因子的增强结合。这些结果确定了克氏锥虫逃避补体介导杀伤的生化基础，并揭示了补体激活的发育调节机制。
During its differentiation in the insect vector to a stage infective for the mammalian host, Trypansoma cruzi becomes resistant to lysis by the alternative pathway of complement. To elucidate the mechanism of complement evasion, we studied control of complement activation on the surface of the noninfective epimastigote and the infective culture-derived metacyclic trypomastigote stages (CMT) of T. cruzi. It was found that the predominant form of complement component C3 on epimastigotes is C3b, whereas the majority of C3 on CMT is in the form of the hemolytically inactive fragment iC3b, which cannot participate in C5 convertase formation or lead to deposition of the lytic C5b-9 complex. Our results also showed that C3 binds by a covalent ester linkage to surface molecules of different molecular weight in the epimastigote stage and CMT. Binding studies with purified complement components indicated that CMT do not support efficient formation of an alternative pathway C3 convertase. C3b on the parasite surface fails to bind the amplification component, factor B, rather than showing enhanced binding of the control component, factor H. These results identify the biochemical basis for evasion of complement-mediated killing in T. cruzi and reveal a mechanism for developmental regulation of complement activation.