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 expressed on the surface of endothelial cells. We examined the role of CD62P in hemorrhagic shock and resuscitation. Rabbits were treated with saline, an anti-CD62P (alpha-CD62P) monoclonal antibody (MAb; PB1.3), an isotype-matched MAb (PNB1.6), or an alpha-CD18 MAb (60.3). Catheters were placed in the femoral artery and vein for monitoring, and cardiac output was then reduced to 33% of baseline for 1.5 h. Shed blood was returned, and resuscitation was continued to maintain the cardiac output to within 90% of baseline. There were no statistical differences between the saline- and MAb PNB1.6-treated groups; they were therefore combined into a control group. The MAb PB1.3- and MAb 60.3-treated groups required significantly less fluid resuscitation than the controls (12, 17, and 56 ml/kg, respectively). We conclude that MAbs directed to functional epitopes of either CD62P or CD18 provide significant protection from vascular injury after hemorrhagic shock.