ANTI-P-SELECTIN MONOCLONAL-ANTIBODY ATTENUATES REPERFUSION INJURY TO THE RABBIT EAR

Neutrophil adherence and / or aggregation has been implicated in ische mia reperfusion injuries. We examined the role of P-selectin in PMN-me diated injury after reperfusion of the rabbit ear. The ear was partial ly amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treat ment was at reperfusion with either saline or one of two murine P-sele ctin mAbs, designated PB1.3 and PNB1.6. mAb PB1.3 cross-reacts with ra bbit P-selectin and prevents histamine-induced leukocyte rolling, wher eas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-select in was detected in the ischemic ear, but not in the nonischemic ear. E ar volume increased to 5.3 times baseline in the saline-treated animal s (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated an imals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treate d animals (n = 8). Estimated tissue necrosis of the combined saline- a nd PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated an imals. We conclude that: (a) P-selectin is expressed in ischemia reper fusion; (b) P-selectin participates in PMN-endothelial cell interactio ns in ischemia reperfusion; and (c) inhibiting P-selectin adhesion sig nificantly reduces reperfusion injury.