PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES ADHERE TO THE PROTEOGLYCAN THROMBOMODULIN IN STATIC AND FLOW-BASED SYSTEMS

Plasmodium falciparum-infected erythrocytes can bind to the glycosamin oglycan chondroitin sulfate A. In this paper, we demonstrate that thro mbomodulin, a proteoglycan present on endothelial cells and placental syncytiotrophoblasts, supports binding of selected lines of P. falcipa rum-infectcd erythrocytes in both static and flow-based assays, and th at adhesion is dependent on the presence of the chondroitin sulfate A chain of thrombomodulin. Chondroitinase treatment of thrombomodulin ab olished binding, and free chondroitin sulfate A prevented it, whereas other soluble glycosaminoglycans had little or no effect. Soluble thro mbomodulin (with. bur not without, its chondroitin sulfate chain) inhi bited binding at 40 mu g/ml, but not at physiological concentrations. Parasitized erythrocytes bound to cells expressing thrombomodulin, inc luding human umbilical vein endothelial cells and A539 cells, and bind ing was inhibited by free chondroitin sulfate A. Established binding t o A549 cells or to immobilized thrombomodulin was substantially revers ed by chondroitin sulfate A at 10 mu g/ml. The chondroitin sulfate cha in of thrombomodulin is a receptor for malaria-infected erythrocytes i n static assays and under physiological flow. (C) 1997 Academic Press.