Time course of airway remodelling after an acute chlorine gas exposure in mice

Accidental chlorine (Cl(2)) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl(2 )exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl(2 )gas. Mice were exposed to 800 ppm Cl(2 )gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl(2 )exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl(2 )exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl(2 )exposure. At 10 days after Cl(2 )exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl(2 )gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.