Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis.
Bleomycin administration results in well-described intracellular oxidative stress that can lead to pulmonary fibrosis. The role of alveolar interstitial antioxidants in this model is unknown. Extracellular superoxide dismutase (EC-SOD) is the primary endogenous extracellular antioxidant enzyme and is abundant in the lung. We hypothesized that EC-SOD plays an important role in attenuating bleomycin-induced lung injury. Two weeks after intratracheal bleomycin administration, we found that wild-type mice induced a 106 +/- 25% increase in lung EC-SOD. Immunohistochemical staining revealed that a large increase in EC-SOD occurred in injured lung. Using mice that overexpress EC-SOD specifically in the lung, we found a 53 +/- 14% reduction in bleomycin-induced lung injury assessed histologically and a 17 +/- 6% reduction in lung collagen content 2 wk after bleomycin administration. We conclude that EC-SOD plays an important role in reducing the magnitude of lung injury from extracellular free radicals after bleomycin administration.
Bowler
Russell P
RP
Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. BowlerR@njc.org
Nicks
Mike
M
Warnick
Karrie
K
Crapo
James D
JD
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D003094:Collagen / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D003094:Collagen; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase