Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats

The objective of this study was to define the influence of hypercholesterolemia on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules. The microvascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more pronounced in hypercholesterolemic rats (compared with control rats). Monoclonal antibodies against the adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-selectin-specific antibody. Platelet aggregation was reduced by antibodies directed against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion-induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte-endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to influence the extravasation of both leukocytes and albumin in postischemic venules of hypercholesterolemic rats.