Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice.
BACKGROUND
Oxidants are believed to play a major role in the development of emphysema.


OBJECTIVE
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.


METHODS
Lung inflammation was measured 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).


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 (Lm, 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.
Foronjy
Robert F
RF
Department of Medicine, Columbia University, 630 West 168th Street, P&S 8-401, New York, NY 10032, USA.
Mirochnitchenko
Oleg
O
Propokenko
Olga
O
Lemaitre
Vincent
V
Jia
Yuxia
Y
Inouye
Masayori
M
Okada
Yasunori
Y
D'Armiento
Jeanine M
JM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D015227:Lipid Peroxidation; D008168:Lung / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000633:toxicity; D009195:Peroxidase / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
D015415:Biomarkers; D009195:Peroxidase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase