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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of a Plasmodium falciparum intercellular adhesion moIecule-1 binding domain: A parasite adhesion trait implicated in cerebral malaria
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Identification of a Plasmodium falciparum intercellular adhesion moIecule-1 binding domain: A parasite adhesion trait implicated in cerebral malaria

机译：恶性疟原虫细胞间粘附moIecule-1结合域的鉴定：与脑疟疾有关的寄生虫粘附特征。

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摘要

Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cere- bral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecuIe-1 (lCAM-1). In this report, we show that Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal lCAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated o. p, y, 5, and e. The DBL domain from the A4tres that binds lCAM-1 is DBLp type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite. contains a DBLp domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBLp do- main from A4var PfEMP1 in lCAM-1 adhesion. The identification of a P falciparum lCAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.
机译：被感染的红细胞与脑小静脉结合是致命性疟疾并发症（脑疟疾）的主要致病事件。与脑隔离相关的唯一寄生虫粘附性状是与细胞间粘附分子1（ICAM-1）结合。在此报告中，我们显示恶性疟原虫红细胞膜蛋白1（PfEMP1）结合ICAM-1。我们已经从A4tres寄生虫克隆并表达了PfEMP1重组蛋白。使用哺乳动物细胞中的异源表达，最小的ICAM-1结合结构域是由第二个达菲结合样（DBL）结合结构域和C2结构域组成的复杂结构域。仅包含任何一个结构域的构建体均不结合ICAM-1。根据系统发育标准，有五种不同的PfEMP1 DBL类型指定为o。 p，y，5和e。绑定lCAM-1的A4tres中的DBL域是DBLp类型。从独特的ICAM-1结合变体A4寄生虫克隆的PfEMP1。包含一个串联排列的DBLp域和一个C2域，类似于A4tres PfEMP1。抗PfEMP1抗血清暗示来自A4var PfEMP1的DBLp域在lCAM-1粘附中。恶性疟原虫lCAM-1结合域的鉴定可以阐明导致脑疟疾发病机理的机制，并导致减少疟疾疾病的干预措施或疫苗的产生。

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