MECHANISMS OF CYTOADHESION OF FLOWING, PARASITIZED RED-BLOOD-CELLS FROM GAMBIAN CHILDREN WITH FALCIPARUM-MALARIA

Adhesion of parasitized red blood cells to vascular endothelium is con sidered to be a major factor in the pathophysiology of falciparum mala ria, and so the molecular mechanisms and theologic characteristics of this interaction are of profound importance. We have investigated the adhesive behavior of wild-type parasite isolates cultured from the blo od of Gambian children with falciparum malaria and allowed to flow ove r surfaces coated with formaldehyde-fixed human umbilical vein endothe lial cells (HUVEC) or platelets. Parasitized cells were able to attach to HUVEC and/or to platelets, and studies with monoclonal antibodies showed that intercellular adhesion molecule-1 (ICAM-1) and CD36 antige n were the major mediators of adhesion for the two surfaces, respectiv ely. The levels of adhesion to HUVEC and to platelets were highly vari able but did not correlate with each other, so that different isolates express independently variable capacities to bind to the two receptor s. Adhesion was stationary for platelets and generally at a higher lev el compared with binding to HUVEC, which was predominantly (about 60%) of a rolling type. The stationary component of adhesion to HUVEC repr esented a greater proportion of adhesion for the wild isolates than fo r laboratory-adapted strains, and this form of adhesion was relatively insensitive to antibody to ICAM-1. This suggests the existence of an additional endothelial cell-expressed receptor for the wild isolates. These studies show wide variation in the ability of wild isolates of P lasmodium falciparum to adhere to ICAM-1, CD36 antigen, and possibly o ther receptors in the presence of physiologically relevant flow. Sever ity of disease may depend on variations in such intrinsic ability, as well as on patterns and levels of expression of the various receptors, which may act cooperatively during sequestration in vivo.