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Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
2013 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, 34-42 p.Article in journal (Refereed) Published
Abstract [en]

Chlorine is highly irritating when inhaled, and is a common toxic industrial gas causing tissue damage in the airways followed by an acute inflammatory response. In this study, we investigated mechanisms by which chlorine exposure may cause reactive airways dysfunction syndrome (RADS) and we examined the dose-dependency of the development of symptoms. Mice were exposed to 50 or 200ppm Cl2 during a single 15min exposure in a nose-only container. The experiment terminated 2, 6, 12, 24, 48, 72h and 7, 14, 28 and 90 days post exposure. Inflammatory cell counts in bronchoalveolar lavage (BAL), secretion of inflammatory mediators in BAL, occurrence of lung edema and histopathological changes in lung tissue was analyzed at each time-point. Airway hyperresponsiveness (AHR) was studied after 24 and 48h and 7, 14, 28 and 90 days. The results showed a marked acute response at 6h (50ppm) and 12h (200ppm) post exposure as indicated by induced lung edema, increased airway reactivity in both central and peripheral airways, and an airway inflammation dominated by macrophages and neutrophils. The inflammatory response declined rapidly in airways, being normalized after 48h, but inflammatory cells were sustained in lung tissue for at least seven days. In addition, a sustained AHR was observed for at least 28 days. In summary, this mouse model of chlorine exposure shows delayed symptoms of hyperreactive airways similar to human RADS. We conclude that the model can be used for studies aimed at improved understanding of adverse long-term responses following inhalation of chlorine.

Place, publisher, year, edition, pages
2013. Vol. 303, 34-42 p.
Keyword [en]
Airway hyperresponsiveness, Chemical-induced lung injury, Chlorine, Mouse model, Respiratory mechanics
National Category
Respiratory Medicine and Allergy
URN: urn:nbn:se:umu:diva-63568DOI: 10.1016/j.tox.2012.10.022OAI: diva2:582160
Available from: 2013-01-03 Created: 2013-01-03 Last updated: 2013-01-03Bibliographically approved

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