title: Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin.
abstract: Adhesion of parasitized erythrocytes to microvascular endothelium is a central event in the pathogenesis of severe falciparum malaria. We have characterized the adhesion of flowing parasitized red blood cells to three of the known endothelial receptors coated on plastic surfaces (CD36, intercellular adhesion molecule-1 (ICAM-1) and thrombospondin (TSP)), and also to cells bearing these receptors (human umbilical vein endothelial cells (HUVEC) and platelets). All of the surfaces could mediate adhesion at wall shear stress within the physiological range. The great majority of adherent parasitized cells formed rolling rather than static attachments to HUVEC and ICAM-1, whereas static attachments predominated for platelets, CD36 and TSP. Studies with monoclonal antibodies verified that binding the HUVEC was mainly via ICAM-1, and to platelets via CD36. Adhesion via ICAM-1 was least sensitive to increasing wall shear stress, but absolute efficiency of adhesion was greatest for CD36, followed by ICAM-1, and least for TSP. TSP did not give long-lasting adhesion under flow, whereas cells remained adherent to CD36 or ICAM-1. We propose that the different receptors may have complementary roles in modulating adhesion in microvessels. Initial interaction at high wall shear stress may be of a rolling type, mediated by ICAM-1 or other receptors, with immobilization and stabilization occurring via CD36 and/or TSP.
authors.affiliation: Department of Haematology, Medical School, University of Birmingham.
authors.forename: B M
authors.initials: BM
authors.lastname: Cooke
authors.forename: A R
authors.initials: AR
authors.lastname: Berendt
authors.forename: A G
authors.initials: AG
authors.lastname: Craig
authors.forename: J
authors.initials: J
authors.lastname: MacGregor
authors.forename: C I
authors.initials: CI
authors.lastname: Newbold
authors.forename: G B
authors.initials: GB
authors.lastname: Nash
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D018955:CD36 Antigens; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010963:Plasmodium falciparum; D013314:Stress, Mechanical; D019699:Thrombospondins
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D018799:Intercellular Adhesion Molecule-1