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.