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

Rogerson, SJ; Chaiyaroj, SC; Ng, K; Reeder, JC; Brown, GV

Author(s): Rogerson, SJ; Chaiyaroj, SC; Ng, K; Reeder, JC; Brown, GV;
Details: Publication Year 1995-07-01,Volume 182,Issue #1,Page 15-20
Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type: Journal Article
Abstract: Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in 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 cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. 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 other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute Co the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: INTERCELLULAR-ADHESION MOLECULE-1; HEPARAN-SULFATE; CIRCUMSPOROZOITE PROTEIN; BEARS RECEPTORS; MALARIA; IDENTIFICATION; CYTOADHERENCE; PROTEOGLYCANS; MEMBRANE; GLYCOPROTEIN
Publisher's Version: https://doi.org/10.1084/jem.182.1.15
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1995-07-01 12:00:00