MECHANISMS UNDERLYING THE MONOCYTE-MEDIATED ANTIBODY-DEPENDENT KILLING OF PLASMODIUM-FALCIPARUM ASEXUAL BLOOD STAGES
MECHANISMS UNDERLYING THE MONOCYTE-MEDIATED ANTIBODY-DEPENDENT KILLING OF PLASMODIUM-FALCIPARUM ASEXUAL BLOOD STAGES
复制标题
DOI：
10.1084/jem.182.2.409
复制
发表时间：
1995-08-01
影响因子：
15.3
通讯作者：
DRUILHE, P
中科院分区：
文献类型：
--
作者：
BOUHAROUNTAYOUN, H;OEUVRAY, C;DRUILHE, P
恶性疟原虫抗体依赖性细胞抑制（ADCI）与临床保护的相关性先前已通过免疫球蛋白G在人体内被动转移保护过程中获得的物质的体外研究确定。我们在此报告进一步的体外研究，旨在阐明这种ADCI效应的机制。目前的研究结果表明：(a)单核细胞（MN）和多形核细胞对卵裂子的摄取对寄生虫病的病程影响不大；(b) ADCI效应是由MN释放的可溶性因子介导的；(c)这个或这些因子能够在单核阶段阻断周围红细胞内寄生虫的分裂；(d)有效抗体靶向的关键触发抗原似乎与分裂子的表面有关，而不是与受感染的红细胞的表面有关；(e)在ADCI中有效的抗体的MN受体显然是Fc γ RII，而不是RI；(f)干扰素- γ和白细胞介素- 4分别上调和下调MN功能；(g)在MN释放的几种潜在介质中，只有肿瘤坏死因子（TNF）被证明与之相关。TNF在防御中的参与可以解释最近描述的TNF-2高表达启动子在流行地区个体中的频率增加，尽管它在严重疟疾中起着不利的作用。
The relevance of the antibody-dependent cellular inhibition (ADCI) of Plasmodium falciparum to clinical protection has been previously established by in vitro studies of material obtained during passive transfer of protection by immunoglobulin G in humans. We here report further in vitro investigations aimed at elucidating the mechanisms underlying this ADCI effect. Results obtained so far suggest that (a) merozoite uptake by monocytes (MN) as well as by polymorphonuclear cells has little influence on the course of parasitemia; (b) the ADCI effect is mediated by a soluble factor released by MN; (c) this or these factors are able to block the division of surrounding intraerythrocytic parasites at the one nucleus stage; (d) the critical triggering antigen(s) targeted by effective Abs would appear to be associated with the surface of merozoites, as opposed to that of infected red blood cells; (e) the MN receptor for Abs effective in ADCI is apparently Fc gamma RII, and not RI; (f) MN function is up- and down-regulated by interferon-gamma and interleukin 4, respectively; and (g) of several potential mediators released by MN, only tumor necrosis factor (TNF) proved of relevance. The involvement of TNF in defense may explain the recently described increased frequency of the TNF-2 high-expression promoter in individuals living in endemic regions despite its compromising role in severe malaria.