On the Cytoadhesion of Plasmodium vivax-Infected Erythrocytes
On the Cytoadhesion of Plasmodium vivax-Infected Erythrocytes
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DOI：
10.1086/654815
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发表时间：
2010-08-15
影响因子：
6.4
通讯作者：
Costa, Fabio T. M.
中科院分区：
文献类型：
--
作者：
Carvalho, Bruna O.;Lopes, Stefanie C. P.;Costa, Fabio T. M.
背景资料。恶性疟原虫和间日疟原虫造成了全球疟疾的大部分负担。虽然恶性疟原虫的致病力增强是由于成熟的红细胞形式在微血管中被隔离，但这种现象在间日疟原虫中尚未被注意到。间日疟原虫感染的严重表现越来越多，与严重恶性疟疾相似，这表明这两种寄生虫的关键致病机制(如细胞黏附)可能是相同的。从34例间日疟原虫感染者的血液中分离出成熟间日疟原虫感染红细胞(PV-IES)。在Percoll梯度上富集的PV-IES用于人肺内皮细胞、Saimiri脑内皮细胞和胎盘冷冻切片的细胞黏附实验。PV-IES能够在静态和流动条件下与表达内皮受体的细胞黏附，已知内皮受体介导恶性疟原虫的细胞黏附。尽管PV-ie细胞黏附水平比观察到的恶性疟原虫感染的红细胞低10倍，但相互作用的强度是相似的。PV-IE的细胞黏附部分是由间日疟原虫变异基因(VIR)编码的VIR蛋白介导的，特异性抗血清可抑制PV-IE与内皮细胞的相互作用。这些观察结果促使对目前疟疾发病机制的范式进行修改，并为研究间日疟原虫感染的病理生理学扫清了道路。
Background. Plasmodium falciparum and Plasmodium vivax are responsible for most of the global burden of malaria. Although the accentuated pathogenicity of P. falciparum occurs because of sequestration of the mature erythrocytic forms in the microvasculature, this phenomenon has not yet been noted in P. vivax. The increasing number of severe manifestations of P. vivax infections, similar to those observed for severe falciparum malaria, suggests that key pathogenic mechanisms (eg, cytoadherence) might be shared by the 2 parasites.Methods. Mature P. vivax-infected erythrocytes (Pv-iEs) were isolated from blood samples collected from 34 infected patients. Pv-iEs enriched on Percoll gradients were used in cytoadhesion assays with human lung endothelial cells, Saimiri brain endothelial cells, and placental cryosections.Results. Pv-iEs were able to cytoadhere under static and flow conditions to cells expressing endothelial receptors known to mediate the cytoadhesion of P. falciparum. Although Pv-iE cytoadhesion levels were 10-fold lower than those observed for P. falciparum-infected erythrocytes, the strength of the interaction was similar. Cytoadhesion of Pv-iEs was in part mediated by VIR proteins, encoded by P. vivax variant genes (vir), given that specific antisera inhibited the Pv-iE-endothelial cell interaction.Conclusions. These observations prompt a modification of the current paradigms of the pathogenesis of malaria and clear the way to investigate the pathophysiology of P. vivax infections.