MECHANISMS RESPONSIBLE FOR ENHANCED INFLAMMATORY RESPONSE TO ISCHEMIA-REPERFUSION IN DIABETES

The objective of the present study was to assess the role of lipid med iators and adhesion molecule expression in exacerbation of ischemia-re perfusion-induced inflammatory response in diabetes. Leukocyte-endothe lial cell interactions were studied in mesenteric venules by intravita l microscopy. Endothelial expression of intercellular adhesion molecul e (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and beta(2)-integrin expression was measured by flow cytom etry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukot riene synthesis inhibitor. Leukotriene B-4 (LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PA F elicited larger increases in diabetic rats. CD11a, but not CD11b, ex pression was higher in leukocytes from diabetic animals. Endothelial I CAM-1 in mesentery and in intestine did not differ between diabetic an d control rats. These results indicate that diabetes is associated wit h an enhanced response to ischemia-reperfusion that depends on both PA F and leukotrienes. An increased sensitivity to PAF, along with an inc reased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.