Time course of lung ischemia-reperfusion-induced ICAM-1 expression and its role in ischemia-reperfusion lung injury.
Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is an important mechanism underlying ischemia-reperfusion (I/R) induced neutrophil activation and tissue injury in other organs. However, I/R of the lungs has not been shown to upregulate ICAM-1 expression. We determined the time course profile of lung I/R-induced ICAM-1 expression and assessed the role of ICAM-1 in mediating neutrophil sequestration, transmigration, and I/R injury in the isolated blood-perfused rat lungs. I/R had a biphasic effect on ICAM-1 expression, an early downregulation and a late-phase upregulation. Superoxide dismutase and neutrophil depletion prevented the early ICAM-1 downregulation. The late-phase ICAM-1 upregulation coincided with the I/R-induced increase in pulmonary microvascular leakage index. ICAM-1 monoclonal antibody (MAb) reversed the I/R-induced increase in pulmonary microvascular leakage index, with control antibody being ineffective. Neither I/R nor ICAM-1 MAb affected lung MPO activity and circulating neutrophil count. Lung I/R significantly increased bronchoalveolar lavage fluid neutrophil count and the GSSG-to-(GSSG+GSH) ratio. ICAM-1 MAb blocked the I/R-induced increase in GSSG-to-(GSSG+GSH) ratio but had no effect on bronchoalveolar lavage fluid neutrophil count. Our results demonstrated that lung I/R up- and downregulates ICAM-1 expression depending on the duration of reperfusion. ICAM-1 upregulation is an important mechanism of I/R-induced pulmonary endothelial injury.
Lu
Yen-Ta
YT
Division of Chest Medicine and Department of Medical Research, Mackay Memorial Hospital, Taipei Medical University, Taipei, Taiwan.
Chen
Pai-Gene
PG
Liu
Shu Fang
SF
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1