CHONDROITIN SULFATE A IS A CELL-SURFACE RECEPTOR FOR PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES

Adherence of Plasmodium falciparum-infected erythrocytes to cerebral p ostcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors me diating adherence have been identified, but the process of adherence i n vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cel ls in a chondroitin sulfate-dependent manner, whereas glycosylation mu tants lacking chondroitin sulfate A (CSA) supported little or no bindi ng. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2 % at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of othe r glycosaminoglycans such as heparan sulfate had no effect. Parasite l ines selected for increased binding to CHO cells and most patient isol ates bound specifically to immobilized CSA. We conclude that P. falcip arum can express or expose proteins at the surface of the infected ery throcyte that mediate specific binding to CSA. This mechanism of adher ence may contribute Co the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the c apacity to bind specifically to cell-associated or immobilized CS.