title: Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear.
abstract: 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 degrees C to 24 degrees 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.
authors.affiliation: Department of Surgery, University of Washington, Seattle.
authors.forename: D
authors.initials: D
authors.lastname: Mihelcic
authors.forename: B
authors.initials: B
authors.lastname: Schleiffenbaum
authors.forename: T F
authors.initials: TF
authors.lastname: Tedder
authors.forename: S R
authors.initials: SR
authors.lastname: Sharar
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
authors.forename: R K
authors.initials: RK
authors.lastname: Winn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D004423:Ear / Q000098:blood supply; D004487:Edema; D019041:L-Selectin; D009336:Necrosis; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000502:physiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019041:L-Selectin; D009195:Peroxidase