Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells
Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells
复制标题
DOI：
10.1086/380761
复制
发表时间：
2004-01-15
影响因子：
6.4
通讯作者：
Grau, GE
中科院分区：
文献类型：
--
作者：
Wassmer, SC;Lépolard, C;Grau, GE
严重疟疾的特点是恶性疟原虫感染的红细胞(IES)被隔离。由于血小板可以影响肿瘤坏死因子(TNF)激活的内皮细胞(ECs)，我们研究了它们在IES隔离中的作用，使用IES，因为它们可以与表达在血小板上的恶性疟原虫受体-内皮CD36(IECD36)黏附。共培养结果表明，血小板可诱导IECD36与CD36缺陷的脑微血管内皮细胞结合。这种诱导的细胞黏附抵抗生理剪切力，被肿瘤坏死因子刺激的内皮细胞增加，并被抗CD36单抗所消除。免疫荧光和扫描电子显微镜结果显示，血小板在IES和内皮细胞表面之间起着桥梁作用，因此可能为黏附到原本缺乏黏附受体的微血管床提供受体。这种新的细胞黏附机制可能重新定位不同寄生虫表型的隔离，并在重症疟疾的发病机制中发挥重要作用。
Severe malaria is characterized by the sequestration of Plasmodium falciparum-infected erythrocytes (IEs). Because platelets can affect tumor necrosis factor (TNF)-activated endothelial cells (ECs), we investigated their role in the sequestration of IEs, using IEs that were selected because they can adhere to endothelial CD36 (IECD36), a P. falciparum receptor that is expressed on platelets. The results of coincubation studies indicated that platelets can induce IECD36 binding to CD36-deficient brain microvascular ECs. This induced cytoadhesion resisted physiological shear stress, was increased by EC stimulation with TNF, and was abolished by anti CD36 monoclonal antibody. Immunofluorescence and scanning electron microscopy results showed that platelets serve as a bridge between IEs and the surface of ECs and may therefore provide receptors for adhesion to microvascular beds that otherwise lack adhesion receptors. This novel mechanism of cytoadhesion may reorient the sequestration of different parasite phenotypes and play an important role in the pathogenesis of severe malaria.