REPERFUSION-INDUCED LEUKOCYTE ADHESION AND VASCULAR PROTEIN LEAKAGE IN NORMAL AND HYPERCHOLESTEROLEMIC RATS

The objective of this study was to define the influence of hypercholes terolemia on ischemia-reperfusion (UR)-induced leukocyte-endothelial c ell adhesion and albumin leakage in rat mesenteric venules. The microv ascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more prono unced in hypercholesterolemic rats (compared with control rats). Monoc lonal antibodies against the adhesion glycoproteins CD11/CD18 and inte rcellular adhesion molecule-1 attenuated the YR-induced leukocyte adhe rence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-select in-specific antibody. Platelet aggregation was reduced by antibodies d irected against either P-selectin, CD18, or intercellular adhesion mol ecule-1, as well as a GPIIb-IIIa antagonist. These results indicate th at the enhanced reperfusion-induced albumin leakage in hypercholestero lemic rats is dependent on leukocyte-endothelial cell adhesion. Furthe rmore, P-selectin- and CD11/CD18- dependent heterotypic and GPIIb-IIIa -mediated homotypic platelet aggregation appear to influence the extra vasation of both leukocytes and albumin in postischemic venules of hyp ercholesterolemic rats.