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Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2012 Sep 01; Vol. 263 (2), pp. 195-202. Date of Electronic Publication: 2012 Jun 19. - Publication Year :
- 2012
-
Abstract
- Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3h) resulted in increased expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24h, expression of HO-1 was biphasic increasing after 3h and 48-72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein-1, inducible nitric oxide synthase and cyclooxygenase-2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Animals
Apoptosis drug effects
Autophagy drug effects
Cell Proliferation drug effects
Deoxyguanosine analogs & derivatives
Deoxyguanosine genetics
Female
Heme Oxygenase-1 genetics
Inflammation chemically induced
Inflammation pathology
Lung pathology
Macrophages, Alveolar pathology
Ozone administration & dosage
Ozone toxicity
Protein C genetics
Rats
Rats, Wistar
Time Factors
Gene Expression Regulation drug effects
Lung drug effects
Macrophages, Alveolar drug effects
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 263
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22727909
- Full Text :
- https://doi.org/10.1016/j.taap.2012.06.009