title: Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling.
abstract: Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.
authors: Departamento de Clínica Médica (LIM 20), Universidade de São Paulo. paolobiselli@usp.br
authors: P J C
authors: PJ
authors: Biselli
authors: F D T Q S
authors: FD
authors: Lopes
authors: H T
authors: HT
authors: Moriya
authors: D H R F
authors: DH
authors: Rivero
authors: A C
authors: AC
authors: Toledo
authors: P H N
authors: PH
authors: Saldiva
authors: T
authors: T
authors: Mauad
authors: M A
authors: MA
authors: Martins
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D014028:Tobacco Smoke Pollution; D016212:Transforming Growth Factor beta; D003094:Collagen