ROLE OF BETA-2 INTEGRINS AND ICAM-1 IN LUNG INJURY FOLLOWING ISCHEMIA-REPERFUSION OF RAT HIND LIMBS

Ischemia/reperfusion involving the hind limbs of rats results in both local injury to skeletal muscle as well as injury to lungs, as measure d by increased vascular permeability (I-125-labeled bovine serum album in leakage) and hemorrhage (extravasation of Cr-51-labeled rat erythro cytes). In the current study, we have focused on events in lungs occur ring during reperfusion of hind limbs. Analysis of blood neutrophils o btained 4 hours after reperfusion has indicated up-regulation of CD11b and CD18 but not CD11a. Plasma from the same animals demonstrate the ability to induce similar effects in normal blood neutrophils, indicat ive of the presence of a neutrophil-activating agent in plasma. During reperfusion, lung injury, which develops progressively over a 4-hour period, has been shown to be neutrophil-dependent and requires CD11a/C D18 and CD11b/CD18 as well as intercellular adhesion molecule-1. These data suggest that ischemia and reperfusion injury of rat lower extrem ities causes systemic changes that result in neutrophil-dependent lung injury that is beta2 integrin- (leukocyte function antigen-1, Mac-1) and intercellular adhesion molecule-1-dependent.