Host receptors for malaria-infected erythrocytes.
Mature trophozoites and schizonts of Plasmodium falciparum induce changes in their host erythrocyte membranes that cause infected erythrocytes to sequester by binding to capillary endothelial cells. Sequestration protects infected erythrocytes from destruction in the spleen and contributes to the pathogenesis of severe and complicated malaria. The use of in vitro parasite culture and cytoadherence assays that measure the binding of infected erythrocytes to target cells has enabled the identification of host proteins that are putative receptors to which infected erythrocytes bind. Three such receptors have been identified: the extracellular matrix protein thrombospondin, the leukocyte differentiation antigen CD36, and the intercellular adhesion molecule ICAM-1. Infected erythrocytes can bind in vitro to each of these proteins. Thrombospondin and CD36 bind to one another, but each also binds to infected erythrocytes independently. Triggering of the CD36 receptor on platelets and monocytes activates these cells in vitro, and stimulation of endothelial cells with cytokines that upregulate ICAM-1 expression can increase the binding of infected erythrocytes to endothelial cells. Studies of these and perhaps other host receptors to which infected erythrocytes bind may contribute to our understanding of pathophysiologic mechanisms in malaria.
Chulay
J D
JD
Walter Reed Army Institute of Research, Washington, DC.
Ockenhouse
C F
CF
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D018955:CD36 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008288:Malaria / Q000097:blood*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology; D019699:Thrombospondins
D000943:Antigens, Differentiation; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D018799:Intercellular Adhesion Molecule-1