Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice

Robert F. Foronjy, Oleg Mirochnitchenko, Olga Propokenko, Vincent Lemaitre, Yuxia Jia, Masayori Inouye, Yasunori Okada, Jeanine M. D'Armiento

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106 Scopus citations

Abstract

Rationale: Oxidants are believed to play a major role in the development of emphysema. Objectives: This study aimed to determine if the expression of human copper-zinc superoxide dismutase (CuZnSOD) within the lungs of mice protects against the development of emphysema. Methods: Transgenic CuZnSOD and littermate mice were exposed to cigarette smoke (6 h/d, 5 d/wk, for 1 yr) and compared with nonexposed mice. A second group was treated with intratracheal elastase to induce emphysema. Measurements: Lung inflammation wasmeasured by cell counts and myeloperoxidase levels. Oxidative damage was assessed by immunofluorescence for 3-nitrotyrosine and 8-hydroxydeoxyguanosine and lipid peroxidation levels. The development of emphysema was determined by measuring the mean linear intercept (Lm). Main Results: Smoke exposure caused a fourfold increase in neutrophilic inflammation and doubled lung myeloperoxidase activity. This inflammatory response did not occur in the smoke-exposed CuZnSOD mice. Similarly, CuZnSOD expression prevented the 58% increase in lung lipid peroxidation products that occurred after smoke exposure. Most important, CuZnSOD prevented the onset of emphysema in both the smoke-induced model (L m, 68 exposed control vs. 58 exposed transgenic; p < 0.04) and elastase-generated model (Lm, 80 exposed control vs. 63 exposed transgenic; p < 0.03). These results demonstrate for the first time that antioxidants can prevent smoke-induced inflammation and can counteract the proteolytic cascade that leads to emphysema formation in two separate animal models of the disease. Conclusions: These findings indicate that strategies aimed at enhancing or supplementing lung antioxidants could be effective for the prevention and treatment of this disease.

Original languageEnglish (US)
Pages (from-to)623-631
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume173
Issue number6
DOIs
StatePublished - Mar 15 2006

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Foronjy, R. F., Mirochnitchenko, O., Propokenko, O., Lemaitre, V., Jia, Y., Inouye, M., Okada, Y., & D'Armiento, J. M. (2006). Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice. American journal of respiratory and critical care medicine, 173(6), 623-631. https://doi.org/10.1164/rccm.200506-850OC