INHIBITION OF CD18-DEPENDENT LEUKOCYTE ADHERENCE BY MAB-6.5 E DOES NOT PREVENT ISCHEMIA-REPERFUSION INJURY AS SEEN IN GRAFTED KIDNEYS

The present study was designed to determine whether beta-2 integrin-me diated leukocyte adherence to the endothelium is involved in renal isc hemia-reperfusion damage and to evaluate the therapeutic intervention potency of monoclonal antibody (mAb) 6.5 E, directed against the leuko cyte CD18 adhesion molecule. To answer these questions, we used a clin ically relevant canine model for the autotransplantation of kidneys th at had been subjected to 30 min of normothermic ischemia, followed by 24 h of cold storage preservation. Intravital fluorescence microscopy of capsular microvessels showed that substantial leukocyte adherence o ccurred after renal ischemia and reperfusion. Leukocyte adherence was observed in both arterioles and venules, but predominantly in the latt er. Reperfusion of the graft resulted in a statistically significant r eduction of the venular red blood cell velocity (RBCV). Moreover, the venular diameter increased. No significant changes in the arteriolar R BCV or in the arteriolar diameter were observed. Administration of mAb 6.5 E, 1 h before reperfusion, inhibited leukocyte adherence to the r enal microvascular endothelium, resulting in an improved venular flow 2 h after reperfusion. However, we observed no beneficial effect of mA b 6.5 E pretreatment on posttransplant graft function and survival. We conclude that leukocyte adherence does not play a critical role in th e development of renal injury following reperfusion of kidneys that ha ve been subjected to prolonged warm and cold ischemia.