Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells.
We have compared the adhesion of Plasmodium falciparum-infected erythrocytes to human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) and have assessed the relative roles of the receptors CD36 and intercellular adhesion molecule-1 (ICAM-1). HUVEC (a cell line that expresses high levels of ICAM-1 but no CD36) mediate low levels of adhesion, whereas HDMEC (which constitutively express CD36) mediate high levels of adhesion even before ICAM-1 induction ICAM-1 expression leads to yet greater levels of adhesion, which are inhibited both by anti-ICAM-1 and CD36 mAbs, despite no increase in the expression of CD36. The results indicate the presence of a substantial population of infected cells that require the presence of both receptors to establish adhesion. Synergy between these receptors could be demonstrated using a number of parasite lines, but it could not be predicted from the binding of these same parasite lines to purified ICAM-1 and CD36. This phenomenon could not be reproduced using either purified receptors presented on plastic, or formalin-fixed HDMEC, suggesting that receptor mobility is important. This is the first study to demonstrate receptor synergy in malaria cytoadherence to human endothelial cells, a phenomenon necessary for parasite survival and associated with disease severity.
McCormick
C J
CJ
Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Craig
A
A
Roberts
D
D
Newbold
C I
CI
Berendt
A R
AR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000469:parasitology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D008297:Male; D008833:Microcirculation; D010963:Plasmodium falciparum / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018955:CD36 Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1