ROLE OF ICAM-1 IN NEUTROPHIL-MEDIATED LUNG VASCULAR INJURY AFTER OCCLUSION AND REPERFUSION

We examined the role of intracellular adhesion molecule 1 (ICAM-1 or CD54) in the development of pulmonary edema in rabbits after pulmonary artery occlusion and reperfusion using a monoclonal antibody (MAb) RR1/1 directed against ICAM-1, a ligand for the CD18 leukocyte adhesion glycoprotein complex. A vascular clamp was placed around the left pulmonary artery for 24 h and then released to allow reperfusion for 2 h. Lungs subjected to 24 h of unilateral pulmonary artery occlusion showed increased binding of I-125-labeled RR1/1 and immunocytochemical evidence of ICAM-1 expression in pulmonary vascular endothelial cells compared with the contralateral lung. MAbs RR1/1 (0.5 mg/kg) or IB4 (1.0 mg/kg) (MAb directed against an epitope on the CD18 adhesion glycoprotein) was infused 45-60 min before the start of reperfusion to assess the roles of ICAM-1 and CD18 in the response. After reperfusion, the lungs were removed, suspended from one end of a weighing balance, and perfused with Ringer-albumin (0.5 g/100 ml), and the changes in lung weight were monitored for 60 min. Lung tissue myeloperoxidase (MPO) content (a marker of neutrophil sequestration) was determined after reperfusion. The increases in lung weight gain in the RR1/1- and IB4-treated groups of 960 +/- 100 and 865 +/- 110 mg, respectively, were less (P < 0.05) than in untreated controls (3,550 +/- 725 mg). Pretreatment with either MAb RR1/1 or IB4 prevented lung neutrophil sequestration as determined by the lung tissue myeloperoxidase content (35.0 +/- 1.7 and 31.5 +/- 2.5 U, respectively) compared with untreated controls (53.0 +/- 2.4 U) (P < 0.05). These results indicate that pulmonary artery occlusion induces pulmonary vascular endothelial ICAM-1 upregulation and that this is a critical factor in pulmonary vascular neutrophil uptake and the resultant pulmonary edema during reperfusion.