Plasmodium falciparum: characterization of adhesion of flowing parasitized red blood cells to platelets.
Adhesion of parasitized red blood cells to vascular endothelium contributes to the ischaemic pathology of severe falciparum malaria. One of the endothelial cytoadhesion receptors, CD36, is also expressed by platelets. We have studied adhesion of flowing parasitized cells to a surface coated with immobilized, activated platelets, both as a model for CD36-mediated adhesion and because interaction with platelets might play a direct role in thrombotic complications of malaria. Parasitized cells were able to bind firmly to platelets over a range of shear stress (up to 0.3 Pa) close to those found in the microcirculation. The binding was largely abolished by treatment of platelets with antibody to CD36, with only a small effect by antibody to ICAM-1. Binding showed pH sensitivity consistent with previous reports of CD36-mediated cytoadhesion. Fixation of the platelet surface with formaldehyde preserved adhesion and its antibody sensitivity, while fixation with glutaraldehyde greatly reduced adhesion and increased the sensitivity to antibody against ICAM-1. Thus CD36-mediated binding is inhibited by glutaraldehyde--but not formaldehyde--fixation, while ICAM-1 can mediate adhesion after either form of fixation. We conclude that platelet-coated surfaces (with or without fixation) represent a practically simple model for studying malarial cytoadhesion and that platelets are likely to be able to bind parasitized cells in vivo and could thus promote vascular occlusion.
Cooke
B M
BM
Department of Haematology, Medical School, University of Birmingham, Edgbaston, United Kingdom.
Nash
G B
GB
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens; D002448:Cell Adhesion; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010963:Plasmodium falciparum / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism
D015703:Antigens, CD; D018955:CD36 Antigens; D010980:Platelet Membrane Glycoproteins