Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1
Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1
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DOI：
10.1073/pnas.93.8.3497
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发表时间：
1996-04-16
影响因子：
11.1
通讯作者：
Pasloske, BL
中科院分区：
文献类型：
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作者：
Baruch, DI;Gormley, JA;Pasloske, BL
成熟的恶性疟原虫寄生红细胞（PRBC）粘附于微血管内皮直接导致急性疟疾病理学。我们使用已知支持PRBC粘附的几种内皮细胞受体，包括CD 36、血小板反应蛋白（TSP）和细胞间粘附分子1（ICAM-1），从表面放射性碘标记的PRBC的去污剂提取物亲和纯化分子，所有三种宿主受体都亲和纯化了恶性疟原虫红细胞膜蛋白1（PfEMP 1），PfEMP 1是一种在粘附的PRBC表面上表达的非常大的疟疾蛋白，PfEMP 1与特定宿主细胞受体的结合与从中提取PfEMP 1的PRBC的结合表型相关，PRBC提取物与抗PfEMP 1抗体、CD 36或TSP的预吸附显著降低PfEMP 1与CD 36或TSP的结合。显示表达抗原性不同的PfEMP 1的恶性疟原虫菌株的完整PRBC的温和胰蛋白酶消化释放不同的I-125标记的PfEMP 1的胰蛋白酶片段，其特异性结合CD 36和TSP。这些活性存在于不同的胰蛋白酶片段上，但是来自克隆ItG-ICAM的单个胰蛋白酶片段与CD 36和TSP结合。因此，CD 36和TSP结合结构域是位于单个PfEMP 1分子上的不同实体。PfEMP 1是感染的红细胞上的疟疾变体抗原，因此是CD 36、TSP和ICAM-1的受体，阻断或逆转PRBC粘附于宿主细胞受体的治疗方法现在可以通过鉴定PfEMP 1作为PRBC粘附于宿主蛋白的疟疾受体来进行。
Adherence of mature Plasmodium falciparum parasitized erythrocytes (PRBCs) to microvascular endothelium contributes directly to acute malaria pathology, We affinity purified molecules from detergent extracts of surface-radioiodinated PRBCs using several endothelial cell receptors known to support PRBC adherence, including CD36, thrombospondin (TSP), and intercellular adhesion molecule 1 (ICAM-1), All three host receptors affinity purified P. falciparum erythrocyte membrane protein 1 (PfEMP1), a very large malarial protein expressed on the surface of adherent PRBCs, Binding of PfEMP1 to particular host cell receptors correlated with the binding phenotype of the PRBCs from which PfEMP1 was extracted, Preadsorption of PRBC extracts with anti-PfEMP1 antibodies, CD36, or TSP markedly reduced PfEMP1 binding to CD36 or TSP, Mild trypsinization of intact PRBCs of P. falciparum strains shown to express antigenically different PfEMP1 released different I-125-labeled tryptic fragments of PfEMP1 that bound specifically to CD36 and TSP, In clone C5 and strain MC, these activities resided on different tryptic fragments, but a single tryptic fragment from clone ItG-ICAM bound to both CD36 and TSP, Hence, the CD36- and TSP-binding domains are distinct entities located on a single PfEMP1 molecule, PfEMP1, the malarial variant antigen on infected erythrocytes, is therefore a receptor for CD36, TSP, and ICAM-1, A therapeutic approach to block or reverse adherence of PRBCs to host cell receptors can now be pursued with the identification of PfEMP1 as a malarial receptor for PRBC adherence to host proteins.