Clonal Variants of Plasmodium falciparum Exhibit a Narrow Range of Rolling Velocities to Host Receptor CD36 under Dynamic Flow Conditions
Clonal Variants of Plasmodium falciparum Exhibit a Narrow Range of Rolling Velocities to Host Receptor CD36 under Dynamic Flow Conditions
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DOI：
10.1128/ec.00148-13
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发表时间：
2013-11-01
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影响因子：
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通讯作者：
Rathod, Pradipsinh K.
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文献类型：
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作者：
Herricks, Thurston;Avril, Marion;Rathod, Pradipsinh K.
恶性疟原虫寄生红细胞(PRBCs)的细胞黏附与疟疾感染的毒力有关。恶性疟原虫红细胞膜蛋白1(PfEMP1)家族介导细胞黏附相互作用。PfEMP1家族处于强烈的抗体和结合选择下，导致胞外结构域的序列和大小发生广泛的变化。在这里，我们研究了在动态流动条件下，pRBC对CD36(恶性疟原虫野外分离株的共同受体)的细胞黏附。在动态流动条件下，使用微流控装置对主要表达单个PfEMP1变体的同源寄生虫与重组CD36的结合进行了评估。我们测试了PfEMP1的大小(胞外结构域的数量)或序列变异是否影响了pRBC-CD36的相互作用。我们的分析表明，尽管存在广泛的PfEMP1序列多态性，但克隆寄生虫变体在CD36滚动速度上的差异接近5倍。此外，贴壁的pRBC在微血管流速下表现出典型的滚动速度滞后，伴随着pRBC形状的变化，可能代表着有利于稳定结合的重要适应。
Cytoadhesion of Plasmodium falciparum parasitized red blood cells (pRBCs) has been implicated in the virulence of malaria infection. Cytoadhesive interactions are mediated by the protein family of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). The PfEMP1 family is under strong antibody and binding selection, resulting in extensive sequence and size variation of the extracellular domains. Here, we investigated cytoadhesion of pRBCs to CD36, a common receptor of P. falciparum field isolates, under dynamic flow conditions. Isogeneic parasites, predominantly expressing single PfEMP1 variants, were evaluated for binding to recombinant CD36 under dynamic flow conditions using microfluidic devices. We tested if PfEMP1 size (number of extracellular domains) or sequence variation affected the pRBC-CD36 interaction. Our analysis showed that clonal parasite variants varied similar to 5-fold in CD36 rolling velocity despite extensive PfEMP1 sequence polymorphism. In addition, adherent pRBCs exhibited a characteristic hysteresis in rolling velocity at microvascular flow rates, which was accompanied by changes in pRBC shape and may represent important adaptations that favor stable binding.