Plasmodium falciparum-infected erythrocytes adhere to the proteoglycan thrombomodulin in static and flow-based systems.
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.
Rogerson
S J
SJ
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Novakovic
S
S
Cooke
B M
BM
Brown
G V
GV
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D018914:Cells, Immobilized; D002809:Chondroitin Sulfates / Q000494:pharmacology; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D008175:Lung Neoplasms; D010963:Plasmodium falciparum / Q000502:physiology*; D018180:Thrombomodulin / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018180:Thrombomodulin; D002809:Chondroitin Sulfates; D002810:Chondroitinases and Chondroitin Lyases