Rogerson S J, Novakovic S, Cooke B M, Brown G V
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Exp Parasitol. 1997 May;86(1):8-18. doi: 10.1006/expr.1996.4142.
Plasmodium falciparum-infected erythrocytes can bind to the glycosaminoglycan chondroitin sulfate A. In this paper, we demonstrate that thrombomodulin, a proteoglycan present on endothelial cells and placental syncytiotrophoblasts, supports binding of selected lines of P. falciparum-infected erythrocytes in both static and flow-based assays, and that adhesion is dependent on the presence of the chondroitin sulfate A chain of thrombomodulin. Chondroitinase treatment of thrombomodulin abolished binding, and free chondroitin sulfate A prevented it, whereas other soluble glycosaminoglycans had little or no effect. Soluble thrombomodulin (with, but not without, its chondroitin sulfate chain) inhibited binding at 40 micrograms/ml, but not at physiological concentrations. Parasitized erythrocytes bound to cells expressing thrombomodulin, including human umbilical vein endothelial cells and A549 cells, and binding was inhibited by free chondroitin sulfate A. Established binding to A549 cells or to immobilized thrombomodulin was substantially reversed by chondroitin sulfate A at 10 micrograms/ml. The chondroitin sulfate chain of thrombomodulin is a receptor for malaria-infected erythrocytes in static assays and under physiological flow.
恶性疟原虫感染的红细胞可与糖胺聚糖硫酸软骨素A结合。在本文中，我们证明，存在于内皮细胞和胎盘合体滋养层细胞上的蛋白聚糖血栓调节蛋白，在静态和基于流动的试验中均支持所选恶性疟原虫感染红细胞系的结合，且这种黏附依赖于血栓调节蛋白硫酸软骨素A链的存在。用软骨素酶处理血栓调节蛋白可消除结合，游离的硫酸软骨素A可阻止结合，而其他可溶性糖胺聚糖几乎没有影响。可溶性血栓调节蛋白（有而非没有其硫酸软骨素链）在40微克/毫升时可抑制结合，但在生理浓度下则不能。被寄生的红细胞与表达血栓调节蛋白的细胞结合，包括人脐静脉内皮细胞和A549细胞，且结合被游离的硫酸软骨素A抑制。已建立的与A549细胞或固定化血栓调节蛋白的结合在10微克/毫升的硫酸软骨素A作用下基本被逆转。在静态试验和生理流动条件下，血栓调节蛋白的硫酸软骨素链是疟疾感染红细胞的受体。
