Gomes Marta T, Monteiro Robson Q, Grillo Luciano A, Leite-Lopes Francisco, Stroeder Heleni, Ferreira-Pereira Antonio, Alviano Celuta S, Barreto-Bergter Eliana, Neto Hugo Castro-Faria, Cunha E Silva Narcisa L, Almeida Igor C, Soares Rosangela M A, Lopes Angela H
Instituto de Microbiologia, Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Cidade Universitária, CCS, Bloco I, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
Int J Parasitol. 2006 Feb;36(2):165-73. doi: 10.1016/j.ijpara.2005.09.016. Epub 2005 Oct 26.
Platelet-activating factor is a phospholipid mediator that exhibits a wide variety of physiological and pathophysiological effects, including induction of inflammatory response, chemotaxis and cellular differentiation. Trypanosoma cruzi, the etiological agent of Chagas' disease, is transmitted by triatomine insects and while in the triatomine midgut the parasite differentiates from a non-infective epimastigote stage into the pathogenic trypomastigote metacyclic form. We have previously demonstrated that platelet activating factor triggers in vitro cell differentiation of T. cruzi. Here we show a platelet activating factor-like activity isolated from lipid extract of T. cruzi epimastigotes incubated in the presence of [14C]acetate. Trypanosoma cruzi-platelet activating factor-like lipid induced the aggregation of rabbit platelets, which was prevented by platelet activating factor-acetylhydrolase. Mouse macrophage infection by T. cruzi was stimulated when epimastigotes were kept for 5 days in the presence of T. cruzi-platelet activating factor, before interacting with the macrophages. The differentiation of epimastigotes into metacyclic trypomastigotes was also triggered by T. cruzi-platelet activating factor. These effects were abrogated by a platelet activating factor antagonist, WEB 2086. Polyclonal antibody raised against mouse platelet activating factor receptor showed labelling for T. cruzi epimastigotes using immunoblotting and immunofluorescence assays. These data suggest that T. cruzi contain the components of an autocrine platelet activating factor-like ligand-receptor system that modulates cell differentiation towards the infectious stage.
血小板活化因子是一种磷脂介质，具有多种生理和病理生理作用，包括诱导炎症反应、趋化作用和细胞分化。克氏锥虫是恰加斯病的病原体，通过锥蝽昆虫传播，在锥蝽中肠内，该寄生虫从非感染性的上鞭毛体阶段分化为致病性的循环后期锥鞭毛体形式。我们之前已经证明血小板活化因子能触发克氏锥虫的体外细胞分化。在此我们展示了从在[14C]乙酸盐存在下孵育的克氏锥虫上鞭毛体的脂质提取物中分离出的一种血小板活化因子样活性。克氏锥虫 - 血小板活化因子样脂质诱导兔血小板聚集，而血小板活化因子乙酰水解酶可阻止这种聚集。当在上鞭毛体与巨噬细胞相互作用之前，将其在克氏锥虫 - 血小板活化因子存在下培养5天时，克氏锥虫对小鼠巨噬细胞的感染会受到刺激。克氏锥虫 - 血小板活化因子也能触发上鞭毛体向循环后期锥鞭毛体的分化。这些作用被血小板活化因子拮抗剂WEB 2086消除。使用免疫印迹和免疫荧光测定法，针对小鼠血小板活化因子受体产生的多克隆抗体显示可标记克氏锥虫上鞭毛体。这些数据表明，克氏锥虫含有一种自分泌血小板活化因子样配体 - 受体系统的成分，该系统可调节细胞向感染阶段的分化。
