RECEPTOR SPECIFICITY OF CLINICAL PLASMODIUM-FALCIPARUM ISOLATES - NONADHERENCE TO CELL-BOUND E-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1

The pathogenicity of Plasmodium falciparum is due largely to the paras ite's unique ability to adhere to capillary and postcapillary venular endothelium during the second half of the 48-hour life cycle, The resu lting sequestration of infected erythrocytes (IRBC) in deep vascular b eds leads to tissue hypoxia, metabolic disturbances, and organ dysfunc tion which characterize severe falciparum malaria, Several endothelial receptors of cytoadherence have been identified, but their clinical r elevance remains controversial, In the present report, the receptor sp ecificity of 60 clinical P falciparum isolates was determined using tr ansfectants each expressing one of CD36, intercellular adhesion molecu le-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM -1). All isolates tested adhered to CD36 and ICAM-1, but the adherence to CD36 was at least 10-fold higher, Seven isolates adhered to E-sele ctin whereas none of 19 isolates adhered to VCAM-1. From a population standpoint, about 30% of IRBC in each isolate adhered to CD36, and 2% to 3% adhered to ICAM-1, The percentage adherent to E-selectin and VCA M-1 was negligible. IRBC selected on CD36 adhered almost exclusively t o CD36 whereas 80% to 90% of IRBC selected on ICAM-1 could also adhere to CD36, Selected IRBC did not adhere to E-selectin or VCAM-1, These findings indicate that cytoadherence to multiple endothelial receptors is a rare occurrence with natural P falciparum isolates, but do not e xclude a role for the adhesion molecules in promoting other IRBC-endot helial interactions such as rolling under flow conditions. Receptor sp ecificity in vivo may be dictated by the ligand-receptor combination w hich provides the best survival potential for the parasite. (C) 1996 b y The American Society of Hematology.