Molecular Basis of Sequestration in Severe and Uncomplicated Plasmodium Falciparum Malaria: Differential Adhesion of Infected Erythrocytes to CD36 and ICAM-1

The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase 125I-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion.