Inhibition of Leukocyte L-Selectin Function With a Monoclonal Antibody Attenuates Reperfusion Injury to the Rabbit Ear

The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia-reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23°C to 24°C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1-3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1-14 MoAb (2 mg/ kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1-3 MoAb-treated group (peak = 25 ± 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 ± 8 mL) and LAM1-14 MoAb-treated (peak = 41 ± 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1-3 MoAb-treated group, whereas significant necrosis (P< .05) was seen in the saline- (8% ± 3% necrosis) and LAM1-14 MoAb-treated (7% ± 3% necrosis) group. We conclude that blocking L-selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.