Short report: Plasmodium falciparum: cytoadherence to alpha(v)beta3 on human microvascular endothelial cells.
Sequestration of infected erythrocytes in brain microvasculature contributes to cerebral malaria, a severe complication of Plasmodium falciparum infection. Sequestration likely involves cytoadherence of parasitized erythrocytes to cerebral microvascular endothelium. Elucidation of the receptors and ligands involved in cytoadherence will likely contribute to a more complete understanding of malaria pathophysiology. The integrin receptor alpha(v)beta3 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 infected with P. falciparum to adhere to alpha(v)beta3 on human microvascular endothelium was investigated. Cytoadherence was quantified under continuous flow at a shear stress of 1.0 dyne/cm2 to mimic shear forces in the cerebral microcirculation. Adherence of erythrocytes infected with P. falciparum to human microvascular endothelial cells was 7-270-fold greater than uninfected erythrocytes. Pretreatment of microvascular endothelial cells with anti-alpha(v) antibody inhibited P. falciparum-infected erythrocyte adherence by 45 +/- 6% (mean +/- SEM). These data suggest that in addition to other endothelial receptors previously described, P. falciparum parasitized red blood cells may bind to the integrin alpha(v)beta3 on microvascular endothelial cells.
Siano
J P
JP
School of Chemical Engineering, Georgia Institute of Technology, Atlanta 30332-0100, USA.
Grady
K K
KK
Millet
P
P
Wick
T M
TM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001667:Binding, Competitive; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology*; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D006801:Humans; D008833:Microcirculation; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D019030:Receptors, Vitronectin / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000098:blood supply
D000906:Antibodies; D019030:Receptors, Vitronectin