期刊
MICROCIRCULATION
卷 14, 期 6, 页码 593-602出版社
WILEY
DOI: 10.1080/10739680701404705
关键词
adhesion molecules; cytoadherence; human/SCID mouse chimeric model; P. falciparum
Cytoadherase of Plasmodium falciparum-infected red blood cells (IRBCs) on human microvascular endothelium is mediated by synergic adhesive interactions with different adhesion molecules in vitro. Here, the authors used a unique human/severe combined immunodeficeint (SCID) mouse chimeric model to directly visualize IRBC-endothelial interactions in an intact human microvasculature in vivo. Stimulation of human skin grafts with 100n TNF-alpha for 4 h led to a dramatic reduction in the distance rolled by IRBC adhered directly to the endothelium with 1.8-fold increase in the number of adherent cells. The decrease in rolling distance and increase in the 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-selection 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 a major contributors to the dynamic process of IRBC adhesion by different mechanisms in vivo.
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