SHORT REPORT - PLASMODIUM-FALCIPARUM - CYTOADHERENCE TO ALPHA(V)BETA(3) ON HUMAN MICROVASCULAR ENDOTHELIAL-CELLS

Sequestration of infected erythrocytes in brain microvasculature contr ibutes to cerebral malaria, a severe complication of Plasmodium falcip arum infection. Sequestration likely involves cytoadherence of parasit ized erythrocytes to cerebral microvascular endothelium. Elucidation o f the receptors and ligands involved in cytoadherence will likely cont ribute to a more complete understanding of malaria pathophysiology. Th e integrin receptor alpha(v)beta(3) is involved in several physiologic and pathologic adherence processes, but its role in cytoadherence has not been investigated. In this study, the ability of erythrocytes inf ected with P. falciparum to adhere to alpha(v)beta(3) on human microva scular endothelium was investigated. Cytoadherence was quantified unde r continuous flow at a shear stress of 1.0 dyne/cm(2) to mimic shear f orces in the cerebral microcirculation. Adherence of erythrocytes infe cted with P. falciparum to human microvascular endothelial cells nias 7-270-fold greater than uninfected erythrocytes. Pretreatment of micro vascular endothelial cells with anti-alpha(v) antibody inhibited P. fa lciparum-infected erythrocyte adherence by 45 +/- 6% (mean +/- SEM). T hese data suggest that in addition to other endothelial receptors prev iously described, P. falciparum parasitized red blood cells may bind t o the integrin alpha(v)beta(3) on microvascular endothelial cells.