ADHESION MOLECULES CONTRIBUTE TO ISCHEMIA AND REPERFUSION-INDUCED INJURY IN THE ISOLATED RAT LUNG

Leukocyte adherence to the endothelium after ischemia and reperfusion contributes to microvascular injury in most organs. The purpose of thi s study was to evaluate the leukocyte and endothelial cell adhesion mo lecules involved with ischemia-reperfusion (I/R)-induced pulmonary mic rovascular injury in the isolated rat lung. After 45 min of ischemia a nd 30 min of reperfusion, microvascular permeability was significantly increased and lung retention of leukocytes occurred. Pretreatment wit h monoclonal antibodies against the leukocyte adhesion molecule CD18 o r the endothelial cell adhesion molecules intercellular adhesion molec ule 1 and P-selectin significantly attenuated the L/R-induced permeabi lity increase and lung sequestration of neutrophils, mononuclear leuko cytes, and eosinophils. In contrast, immunoneutralization of the rat l eukocyte adhesion molecule L-selectin neither protected against the I/ R-induced permeability increase nor prevented lung sequestration of ne utrophils and eosinophils. We conclude that leukocyte adherence in the pulmonary, microvasculature and subsequent permeability increase afte r I/R is dependent on the integrin CD18, its endothelial cell ligand i ntercellular adhesion molecule 1, and the endothelial cell rolling fac tor P-selectin but not the leukocyte rolling factor L-selectin.