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克氏锥虫锥鞭毛体对替代补体途径溶解作用的抗性机制:特异性单克隆抗体的影响

Mechanism of resistance to lysis by the alternative complement pathway in Trypanosoma cruzi trypomastigotes: effect of specific monoclonal antibody.

作者信息

Schenkman S, Güther M L, Yoshida N

出版信息

J Immunol. 1986 Sep 1;137(5):1623-8.

PMID:2943798
Abstract

Trypanosoma cruzi G strain epimastigotes were lysed by normal human serum (NHS) through activation of the alternative complement pathway (ACP), whereas metacyclic trypomastigotes were resistant to lysis. Epimastigotes and metacyclics with equivalent amounts of C3b deposited on their surface bound factor B with similar affinities. In contrast, factor H bound with higher affinity to metacyclics than to epimastigotes. Both T. cruzi forms with bound C3b were extensively (60 to 80%) lysed after formation of surface C3-convertase and the addition of a C3-C9 complement source. In the presence of factors H and I, or incubation with NHS with EDTA, the percentage of lysis of metacyclics decreased faster than that of epimastigotes with increasing incubation times. These data suggest, as a possible mechanism of resistance to lysis in metacyclic trypomastigotes, the higher binding affinity of factor H to C3b and the inactivation of the latter by serum regulatory proteins. Metacyclics were lysed by NHS, through ACP, in the presence of human immune serum to T. cruzi or anti-T. cruzi monoclonal antibody, but not with the Fab fragment of the latter, which recognizes a 90,000 m.w. antigen from T. cruzi metacyclics. Protection of parasite-bound C3b from serum control proteins was observed when parasites were incubated, before C3 deposition, with the lytic monoclonal antibody but not with its Fab fragment or a nonrelated IgG control. When C3b was deposited on metacyclics before antibody binding, C3b inactivation occurred. In the lysis of metacyclics, through ACP activation, binding of antibody apparently creates new acceptor sites which prevent the activity of serum regulatory proteins.

摘要

克氏锥虫G株无鞭毛体可被正常人血清(NHS)通过激活替代补体途径(ACP)溶解,而循环后期锥鞭毛体对溶解具有抗性。表面沉积等量C3b的无鞭毛体和循环后期锥鞭毛体以相似的亲和力结合B因子。相比之下,H因子与循环后期锥鞭毛体的结合亲和力高于与无鞭毛体的结合亲和力。两种结合了C3b的克氏锥虫形式在表面C3转化酶形成并添加C3 - C9补体来源后均被大量(60%至80%)溶解。在存在H因子和I因子的情况下,或用含EDTA的NHS孵育时,随着孵育时间增加,循环后期锥鞭毛体的溶解百分比比无鞭毛体下降得更快。这些数据表明,作为循环后期锥鞭毛体抗溶解的一种可能机制,H因子对C3b的结合亲和力更高,且血清调节蛋白可使后者失活。在存在针对克氏锥虫的人免疫血清或抗克氏锥虫单克隆抗体的情况下,循环后期锥鞭毛体可被NHS通过ACP溶解,但不能被后者的Fab片段溶解,该Fab片段识别来自克氏锥虫循环后期锥鞭毛体的一种90,000分子量的抗原。当寄生虫在C3沉积前与溶细胞单克隆抗体而非其Fab片段或无关IgG对照孵育时,观察到寄生虫结合的C3b受到血清控制蛋白的保护。当在抗体结合前C3b沉积在循环后期锥鞭毛体上时,C3b发生失活。在通过ACP激活溶解循环后期锥鞭毛体的过程中,抗体的结合显然会产生新的受体位点,从而阻止血清调节蛋白的活性。

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