Differential roles of CD36, ICAM-1, and P-selectin in Plasmodium falciparum cytoadherence in vivo.
Cytoadherence of Plasmodium falciparum-infected red blood cells (IRBCs) on human microvascular endothelium is mediated by synergistic adhesive interactions with different adhesion molecules in vitro. Here, the authors used a unique human/severe combined immunodeficient (SCID) mouse chimeric model to directly visualize IRBC-endothelial interactions in an intact human microvasculature in vivo. Stimulation of human skin grafts with 100 ng TNF-alpha for 4 h led to a dramatic reduction in the distance rolled by IRBCs before arrest, so that the majority of IRBCs adhered directly to the endothelium with a 1.8-fold increase in the number of adherent cells. The decrease in rolling distance and increase in adhesion could be reversed by anti-ICAM-1. More importantly, the effect of TNF-alpha could be seen only in the presence of CD36. A further increase in adhesion by 4.9-fold was observed after 24 h of TNF-alpha stimulation. The increase could be reversed by anti-ICAM-1, but not anti-VCAM-1. In histamine-stimulated grafts, the rolling flux fraction and adhesion increased by 2.8- and 1.6-fold, respectively. The increases were attributable to P-selectin as an inhibitory anti-P-selectin antibody abrogated both the increased rolling flux fraction and firm adhesion. These findings indicate that in addition to CD36, ICAM-1, and P-selectin are major contributors to the dynamic process of IRBC adhesion by different mechanisms in vivo.
Yipp
Bryan G
BG
Department of Microbiology and Infectious Diseases, University of Calgary, Alberta, Canada.
Hickey
Michael J
MJ
Andonegui
Graciela
G
Murray
Allan G
AG
Looareesuwan
Sornchai
S
Kubes
Paul
P
Ho
May
M
D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D002678:Chimera; D004730:Endothelium, Vascular / Q000473:pathology; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D051379:Mice; D008833:Microcirculation / Q000469:parasitology / Q000473:pathology; D019007:P-Selectin / Q000502:physiology*; D010963:Plasmodium falciparum / Q000472:pathogenicity*
D018955:CD36 Antigens; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1