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Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis.

Abstract
Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced fibrosis of larger airways that developed by day 7 after exposure and was associated with airway hyperreactivity. In contrast, A/J mice had little or no airway fibrosis and had normal lung function at day 7. Unexposed FVB/NJ mice had less keratin 5 staining (basal cell marker) than A/J mice in large intrapulmonary airways where epithelial repair was poor and fibrosis developed after chlorine exposure. FVB/NJ mice had large areas devoid of epithelium on day 1 after exposure leading to fibroproliferative lesions on days 4 and 7. A/J mice had airways covered by squamous keratin 5-stained cells on day 1 that transitioned to a highly proliferative reparative epithelium by day 4 followed by the reappearance of ciliated and Clara cells by day 7. The data suggest that lack of basal cells in the large intrapulmonary airways and failure to effect epithelial repair at these sites are factors contributing to the development of airway fibrosis in FVB/NJ mice. The observed differences in susceptibility to chlorine-induced airway disease provide a model in which mechanisms and treatment of airway fibrosis can be investigated.
AuthorsYiqun Mo, Jing Chen, Connie F Schlueter, Gary W Hoyle
JournalAmerican journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 304 Issue 2 Pg. L92-102 (Jan 15 2013) ISSN: 1522-1504 [Electronic] United States
PMID23171502 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Chlorine
  • Collagen
Topics
  • Acute Lung Injury (chemically induced)
  • Animals
  • Bronchoalveolar Lavage Fluid (cytology)
  • Chlorine (adverse effects, toxicity)
  • Collagen (metabolism)
  • Fibrosis (chemically induced)
  • Lung (drug effects, pathology)
  • Lung Diseases
  • Male
  • Mice

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