Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells

Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells
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DOI:
10.1172/jci119794
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发表时间:
1997-11-15
影响因子:
15.9
通讯作者:
Berendt, AR
Berendt, AR
中科院分区:
医学1区
文献类型:
--
作者:
McCormick, CJ;Craig, A;Berendt, AR

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我们比较了恶性疟原虫感染的红细胞粘附到人真皮微血管内皮细胞(HDMEC)和人脐静脉内皮细胞(HUVEC),并评估了受体CD 36和细胞间粘附分子-1(ICAM-1)的相对作用。HUVEC(一种表达高水平ICAM-1但不表达CD 36的细胞系)介导低水平的粘附,而HDMEC(其组成性表达CD 36)甚至在ICAM-1诱导之前介导高水平的粘附,ICAM-1表达导致更高水平的粘附,其被抗ICAM-1和CD 36 mAb抑制,尽管CD 36的表达没有增加,结果表明,存在大量需要两种受体存在以建立粘附的感染细胞。这些受体之间的协同作用可以证明使用一些寄生虫线,但它不能从这些相同的寄生虫线的结合纯化的ICAM-1和CD 36预测。这种现象不能再现使用任何纯化的受体上提出的塑料,或福尔马林固定的HDMEC,表明受体的流动性是重要的。这是第一个研究证明疟疾细胞粘附到人类内皮细胞,寄生虫生存所必需的现象,并与疾病的严重程度相关的受体协同作用。
We have compared the adhesion of Plasmodium falciparum-infected erythrocytes to human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) and have assessed the relative roles of the receptors CD36 and intercellular adhesion molecule-1 (ICAM-1). HUVEC (a cell line that expresses high levels of ICAM-1 but no CD36) mediate low levels of adhesion, whereas HDMEC (which constitutively express CD36) mediate high levels of adhesion even before ICAM-1 induction, ICAM-1 expression leads to yet greater levels of adhesion, which are inhibited both by anti-ICAM-1 and CD36 mAbs, despite no increase in the expression of CD36, The results indicate the presence of a substantial population of infected cells that require the presence of both receptors to establish adhesion. Synergy between these receptors could be demonstrated using a number of parasite lines, but it could not be predicted from the binding of these same parasite lines to purified ICAM-1 and CD36. This phenomenon could not be reproduced using either purified receptors presented on plastic, or formalin-fixed HDMEC, suggesting that receptor mobility is important. This is the first study to demonstrate receptor synergy in malaria cytoadherence to human endothelial cells, a phenomenon necessary for parasite survival and associated with disease severity.