Published ahead of print on April 30, 2003, doi:10.1164/rccm.200201-021OC Am. J. Respir. Crit. Care Med., Volume 168, Number 5, September 2003, 568-574 A more recent version of this article appeared on September 1, 2003
Submitted on January 11, 2002 Chlorine-induced injury to the airways in the mouseJames G Martin1*,1 Meakins-Christie Laboratories, Montreal, Quebec, Canada; Medicine, McGill University, Montreal, Quebec, Canada, 2 Respiratory Division, Hopital Sacre Coeur, Montreal, Quebec, Canada; University of Montreal, Montreal, Quebec, Canada, 3 Meakins-Christie Laboratories, Montreal, Quebec, Canada, 4 Meakins-Christie Laboratories, Montreal, Quebec, Canada; University of Montreal, Montreal, Quebec, Canada * To whom correspondence should be addressed. E-mail: james.martin{at}mcgill.ca.
Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice at 24 h after a 5 minute exposure to 100, 200, 400 or 800 ppm Cl2 and at 2 and 7 days after 400 ppm Cl2 inhalation. Airway responsiveness was higher 24 h after 400 ppm and 800 ppm Cl2. Responsiveness following 400 ppm returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase (iNOS) expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of iNOS with 1400W (1mg/kg) abrogated the Cl2 induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. iNOS is involved in the induction of changes in responsiveness to methacholine. Key words: chlorine, oxidative injury, nitric oxide synthase, nitric oxide
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