title: Neutrophils are not necessary for induction of ischemia-reperfusion lung injury.
abstract: Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
authors.forename: G M
authors.initials: GM
authors.lastname: Deeb
authors.forename: C M
authors.initials: CM
authors.lastname: Grum
authors.forename: M J
authors.initials: MJ
authors.lastname: Lynch
authors.forename: T P
authors.initials: TP
authors.lastname: Guynn
authors.forename: K P
authors.initials: KP
authors.lastname: Gallagher
authors.forename: A G
authors.initials: AG
authors.lastname: Ljungman
authors.forename: S F
authors.initials: SF
authors.lastname: Bolling
authors.forename: M L
authors.initials: ML
authors.lastname: Morganroth
mesh_terms: D000818:Animals; D002374:Catalase / Q000494:pharmacology; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D002374:Catalase; D010100:Oxygen