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 125I-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 less than 0.05) than in untreated controls (3,550 +/- 725 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, Albany Medical College, New York 12208.
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MJ
Horgan
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Ge
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Gu
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Rothlein
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Malik
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010208:Papaverine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D010208:Papaverine