title: A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice.
abstract: Oxidative stress plays a role in the pathophysiology of emphysema through the activation of tissue proteases and apoptosis. We examined the effects of ozone exposure by exposing BALB/c mice to either a single 3-h exposure or multiple exposures over 3 or 6 wk, with two 3-h exposures per week. Compared with air-exposed mice, the increase in neutrophils in bronchoalveolar lavage fluid and lung inflammation index was greatest in mice exposed for 3 and 6 wk. Lung volumes were increased in 3- and 6-wk-exposed mice but not in single-exposed. Alveolar space and mean linear intercept were increased in 6- but not 3-wk-exposed mice. Caspase-3 and apoptosis protease activating factor-1 immunoreactivity was increased in the airway and alveolar epithelium and macrophages of 3- and 6-wk-exposed mice. Interleukin-13, keratinocyte chemoattractant, caspase-3, and IFN-γ mRNA were increased in the 6-wk-exposed group, but heme oxygenase-1 (HO-1) mRNA decreased. matrix metalloproteinase-12 (MMP-12) and caspase-3 protein expression increased in lungs of 6-wk-exposed mice. Collagen area increased and epithelial area decreased in airway wall at 3- and 6-wk exposure. Exposure of mice to ozone for 6 wk induced a chronic inflammatory process, with alveolar enlargement and damage linked to epithelial apoptosis and increased protease expression.
authors.affiliation: Experimental Studies Unit, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Kostas
authors.initials: K
authors.lastname: Triantaphyllopoulos
authors.forename: Farhana
authors.initials: F
authors.lastname: Hussain
authors.forename: Mariona
authors.initials: M
authors.lastname: Pinart
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.forename: Paul
authors.initials: P
authors.lastname: Kirkham
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010126:Ozone; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects
chemical_list: D010126:Ozone; D051547:Heme Oxygenase-1; D053148:Caspase 3; D053508:Matrix Metalloproteinase 12