title: Increased sensitivity to asbestos-induced lung injury in mice lacking extracellular superoxide dismutase.
abstract: Asbestosis is a chronic form of interstitial lung disease characterized by inflammation and fibrosis that results from the inhalation of asbestos fibers. Although the pathogenesis of asbestosis is poorly understood, reactive oxygen species may mediate the progression of this disease. The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) can protect the lung against a variety of insults; however, its role in asbestosis is unknown. To determine if EC-SOD plays a direct role in protecting the lung from asbestos-induced injury, intratracheal injections of crocidolite were given to wild-type and ec-sod-null mice. Bronchoalveolar lavage fluid (BALF) from asbestos-treated ec-sod-null mice at 24 h, 14 days, or 28 days posttreatment showed increased inflammation and total BALF protein content compared to that of wild-type mice. In addition, lungs from ec-sod-null mice showed increased hydroxyproline content compared to those of wild-type mice, indicating a greater fibrotic response. Finally, lungs from ec-sod-null mice showed greater oxidative damage, as assessed by nitrotyrosine content compared to those of their wild-type counterparts. These results indicate that depletion of EC-SOD from the lung increases oxidative stress and injury in response to asbestos.
authors.affiliation: Department of Pathology, University of Pittsburgh, S740 Scaife Hall, 3550 Terrace St., Pittsburgh, PA 15261, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Fattman
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Tan
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Tobolewski
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
mesh_terms: D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D017638:Asbestos, Crocidolite; C002744:3-nitrotyrosine; D014443:Tyrosine; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D006909:Hydroxyproline