ROLLING AND STATIONARY CYTOADHESION OF RED-BLOOD-CELLS PARASITIZED BYPLASMODIUM-FALCIPARUM - SEPARATE ROLES FOR ICAM-1, CD36 AND THROMBOSPONDIN

Adhesion of parasitized erythrocytes to microvascular endothelium is a central event in the pathogenesis of severe falciparum malaria. We ha ve characterized the adhesion of flowing parasitized red blood cells t o three of the known endothelial receptors coated on plastic surfaces (CD36, intercellular adhesion molecule-1 (ICAM-1) and thrombospondin ( TSP)), and also to cells bearing these receptors (human umbilical vein endothelial cells (HUVEC) and platelets). All of the surfaces could m ediate adhesion at wall shear stress within the physiological range. T he great majority of adherent parasitized cells formed rolling rather than static attachments to HUVEC and ICAM-1, whereas static attachment s predominated for platelets, CD36 and TSP. Studies with monoclonal an tibodies verified that binding the HUVEC was mainly via ICAM-1, and to platelets via CD36. Adhesion via ICAM-1 was least sensitive to increa sing wall shear stress, but absolute efficiency of adhesion was greate st for CD36, followed by ICAM-1, and least for TSP. TSP did not give l ong-lasting adhesion under now, whereas cells remained adherent to CD3 6 or ICAM-1. We propose that the different receptors may have compleme ntary roles in modulating adhesion in microvessels. Initial interactio n at high wall shear stress may be of a rolling type, mediated by ICAM -1 or other receptors, with immobilization and stabilization occurring via CD36 and/or TSP.