Three adhesion receptor families appear important in mediating pulmonary leukocyte trafficking. The selection family of receptors initiate early leukocyte/endothelial interactions, while the integrin and immunoglobulin families interact in later interactions. We previously found that monoclonal antibodies (MAbs) directed against the integrin family of adhesion molecules limited pulmonary injury and improved survival related to tumor necrosis function challenge in canines. However, administration of integrin MAbs during bacterial peritonitis in a canine model reduced serum endotoxin clearance and worsened cardiovascular function and survival. During pulmonary infection in rats, similar MAbs were beneficial in limiting pulmonary injury, but still worsened survival. In additional studies we showed that ICAM-1-directed MAbs were also harmful during intrapulmonary infection. These studies have emphasized the importance of both integrin and ICAM-1 adhesion receptors in host defense during pneumonia. To complete these studies, we investigated the effects of MAbs directed against L-selectin, a member of the third family of adhesion receptors. Although improving survival with intravascular E. coli challenge in this study, L-selectin-directed MAb worsened survival with pulmonary infection. We are presently performing additional studies to determine how site of infection alters the effects of L-selectin-directed MAbs in our small animal model of sepsis.
