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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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
Pages (from-to)623-631
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume173
Issue number6
DOIs
Publication statusPublished - 2006 Mar 15

Fingerprint

Pancreatic Elastase
Emphysema
Smoke
Tobacco Products
Superoxide Dismutase
Lung
Lipid Peroxidation
Peroxidase
Pneumonia
Antioxidants
Animal Disease Models
Oxidants
Fluorescent Antibody Technique
Zinc
Copper
Cell Count
Inflammation

Keywords

  • Emphysema
  • Inflammation
  • Oxidants

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Foronjy, R. F., Mirochnitchenko, O., Propokenko, O., Lemaitre, V., Jia, Y., Inouye, M., ... 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

Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice. / Foronjy, Robert F.; Mirochnitchenko, Oleg; Propokenko, Olga; Lemaitre, Vincent; Jia, Yuxia; Inouye, Masayori; Okada, Yasunori; D'Armiento, Jeanine M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 173, No. 6, 15.03.2006, p. 623-631.

Research output: Contribution to journalArticle

Foronjy, RF, Mirochnitchenko, O, Propokenko, O, Lemaitre, V, Jia, Y, Inouye, M, Okada, Y & D'Armiento, JM 2006, 'Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice', American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 6, pp. 623-631. https://doi.org/10.1164/rccm.200506-850OC
Foronjy, Robert F. ; Mirochnitchenko, Oleg ; Propokenko, Olga ; Lemaitre, Vincent ; Jia, Yuxia ; Inouye, Masayori ; Okada, Yasunori ; D'Armiento, Jeanine M. / Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice. In: American Journal of Respiratory and Critical Care Medicine. 2006 ; Vol. 173, No. 6. pp. 623-631.
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