Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium
Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium
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DOI：
10.1096/fj.09-135822
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Grau, Georges E.
中科院分区：
文献类型：
--
作者：
Faille, Dorothee;Combes, Valery;Grau, Georges E.
脑型疟疾（CM）的特征是脑微血管内循环细胞的积聚，其中血小板起着重要作用。在体外，血小板调节恶性疟原虫寄生的红细胞（PRBCs）对脑内皮细胞的细胞粘附。在这里，我们首次表明，血小板微粒（PMP）能够结合PRBC，从而将血小板抗原转移到PRBC表面。这种结合在很大程度上是PRBC特异性的，因为PMP对正常红细胞几乎没有粘附。PMP粘附也依赖于PRBC表达的恶性疟原虫红细胞膜蛋白1变体。PMP与PRBC的结合在PRBC表面蛋白被胰蛋白酶中和后或在用抗血小板内皮细胞粘附分子-1（CD 31）和糖蛋白IV（CD 36）的mAb处理PMP后降低。此外，PMP摄取是一个动态过程，可以通过人脑内皮细胞（HBEC）实现，诱导内皮表型的变化。最后，PMP显著增加PRBC对HBEC的细胞粘附。总之，我们的研究确定了几种机制，PMPs可能参与CM发病机制，同时与PRBCs和HBECs相互作用。因此，PMPs为拮抗血管细胞之间的相互作用提供了一种新的靶点，这种相互作用促进了CM期间的微血管淤积和血脑屏障改变。Faille，D.，Combes，V.米切尔，A. J.，方丹，朱汉-维格岛Alessi，M. C.的方法，Chimini，G.，Fusa，T.，格劳湾E.血小板微粒：疟疾寄生虫细胞粘附人脑内皮细胞的新参与者。FASEB J.23，3449-3458（2009）. www.fasebj.org
Cerebral malaria ( CM) is characterized by accumulation of circulating cells within brain microvessels, among which platelets play an important role. In vitro, platelets modulate the cytoadherence of Plasmodium falciparum-parasitized red blood cells (PRBCs) to brain endothelial cells. Here we show for the first time that platelet microparticles (PMPs) are able to bind to PRBCs, thereby transferring platelet antigens to the PRBC surface. This binding is largely specific to PRBCs, because PMPs show little adherence to normal red blood cells. PMP adherence is also dependent on the P. falciparum erythrocyte membrane protein 1 variant expressed by PRBCs. PMP binding to PRBCs decreases after neutralization of PRBC surface proteins by trypsin or after treatment of PMPs with a mAb to platelet-endothelial cell adhesion molecule-1 (CD31) and glycoprotein IV (CD36). Furthermore, PMP uptake is a dynamic process that can be achieved by human brain endothelial cells (HBECs), inducing changes in the endothelial phenotype. Lastly, PMPs dramatically increase PRBC cytoadherence to HBECs. In conclusion, our study identifies several mechanisms by which PMPs may participate in CM pathogenesis while interacting with both PRBCs and HBECs. PMPs thereby provide a novel target for antagonizing interactions between vascular cells that promote microvascular sludging and blood brain barrier alteration during CM.-Faille, D., Combes, V., Mitchell, A. J., Fontaine, A., Juhan-Vague, I., Alessi, M.-C., Chimini, G., Fusa, T., Grau, G. E. Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. FASEB J. 23, 3449-3458 ( 2009). www.fasebj.org