A MONOCLONAL-ANTIBODY TO P-SELECTIN AMELIORATES INJURY ASSOCIATED WITH HEMORRHAGIC-SHOCK IN RABBITS

P-selectin (CD62P) can participate in leukocyte rolling when it is exp ressed on the surface of endothelial cells. We examined the role of CD 62P in hemorrhagic shock and resuscitation. Rabbits were treated with saline, an anti-CD62P (alpha-CD62P) monoclonal antibody (MAb; PB1.3), an isotype-matched hSAb (PNB1.6), or an alpha-CD18 MAb (60.3). Cathete rs were placed in the femoral artery and vein for monitoring, and card iac output was then reduced to 33% of baseline for 1.5 h. Shed blood w as returned, and resuscitation was continued to maintain the cardiac o utput to within 90% of baseline. There were no statistical differences between the saline- and MAb PNB1.6-treated groups; they were therefor e combined into a control group. The MAb PB1.3- and MAb 60.3-treated g roups required significantly less fluid resuscitation than the control s (12, 17, and 56 ml/kg, respectively). We conclude that MAbs directed to functional epitopes of either CD62P or CD18 provide significant pr otection from vascular injury after hemorrhagic shock.