title: Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium.
abstract: Xanthine oxidase (XO)-generated toxic O2 metabolites appear to contribute to reperfusion injury, but the possibility that XO is involved in hyperoxic or neutrophil elastase-mediated injury has not been investigated. We found that lungs isolated from rats fed a tungsten-rich diet had negligible XO activities and after exposure to hyperoxia developed less acute edematous injury during perfusion with buffer or purified neutrophil elastase than XO-replete lungs from control rats which had been exposed to hyperoxia. In parallel, tungsten-treated XO-depleted cultured bovine pulmonary arterial endothelial cells made less superoxide anion and as monolayers leaked less 125I-labeled albumin after exposure to neutrophil elastase than XO-replete endothelial cell monolayers. Our findings suggest that XO-derived O2 metabolites contribute to acute edematous lung injury from hyperoxia directly and by enhancing susceptibility to neutrophil elastase.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: T C
authors.initials: TC
authors.lastname: Rodell
authors.forename: J C
authors.initials: JC
authors.lastname: Cheronis
authors.forename: C L
authors.initials: CL
authors.lastname: Ohnemus
authors.forename: D J
authors.initials: DJ
authors.lastname: Piermattei
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010100:Oxygen / Q000633:toxicity; D010196:Pancreatic Elastase / Q000633:toxicity; D011654:Pulmonary Edema / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D013481:Superoxides; D014969:Xanthine Oxidase; D010196:Pancreatic Elastase; D010100:Oxygen; D014414:Tungsten