Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2
Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2
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DOI：
10.1182/blood-2002-12-3710
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发表时间：
2003-06-15
期刊：
影响因子：
20.3
通讯作者：
Gysin, J
中科院分区：
文献类型：
--
作者：
Douki, JBL;Sterkers, Y;Gysin, J
最近的研究结果已经挑战了目前的观点恶性疟原虫（P falciparum）血液阶段的生物学证明早期环阶段感染的红细胞（rIEs）宿主内皮细胞和胎盘合胞体滋养层细胞的细胞粘附。仅在通过硫酸软骨素A（CSA）与胎盘结合的寄生虫中观察到rIE的粘附。在这项工作中，产生了一组特异性抑制rIE细胞粘附但不抑制成熟IE细胞粘附的小鼠单克隆抗体（mAb）。先前描述的环表面蛋白2（RSP-2），一种42-kDa蛋白，被鉴定为环阶段特异性mAb的靶标。时程表面荧光实验显示，RSP-2和恶性疟原虫红细胞膜蛋白1（PfEMP 1）之间的表达短的重叠（约4小时）。它们的连续表达使得IE能够在整个血液阶段周期中粘附于内皮细胞。在这项研究中，在寄生虫培养物中检测到一种新的表型，即正常红细胞（内斯）与内皮细胞的粘附。所有粘附的内斯均用RSP-2包被。免疫定位研究表明，RSP-2是一种棒状体衍生的蛋白质，在与裂殖子接触期间被释放到红细胞膜上。我们的研究结果确定RSP-2作为一个关键分子在隔离的年轻的血液阶段的形式和内斯内皮细胞。(C)2003年，美国血液学会。
Recent findings have challenged the current view of Plasmodium falciparum (P falciparum) blood-stage biology by demonstrating the cytoadhesion of early ring-stage-infected erythrocytes (rIEs) to host endothelial cells and placental syncytiotrophoblasts. The adhesion of rIEs was observed only in parasites that bind to the placenta via chondroitin sulfate A (CSA). In this work, a panel of mouse monoclonal antibodies (mAbs) that specifically inhibit cytoadhesion of rIEs but not of mature IEs was generated. The previously described ring surface protein 2 (RSP-2), a 42-kDa protein, was identified as the target of the ring-stage-specific mAbs. Time course surface fluorescence experiments revealed a short overlap (approximately 4 hours) of expression between RSP-2 and P falciparum erythrocyte membrane protein 1 (PfEMP1). Their consecutive expression enables IEs to adhere to endothelial cells during the entire blood-stage cycle. During this study, a new phenotype was detected in parasite cultures, the adhesion of normal erythrocytes (nEs) to endothelial cells. All adherent nEs were coated with RSP-2. Immunolocalization studies show that RSP-2 is a rhoptry-derived protein that is discharged onto the erythrocyte membrane during contact with merozoites. Our results identify RSP-2 as a key molecule in sequestration of young bloodstage forms and nEs to endothelial cells. (C) 2003 by The American Society of Hematology.