The role of gamma delta T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice.
Koohsari-H; Tamaoka-M; Campbell-HR; Martin-JG
Respir Res 2007 Mar; 8:21
BACKGROUND: Acute exposure to chlorine (Cl2) gas causes epithelial injury and airway dysfunction. gammadelta T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium. METHODS: C57Bl/6J (wild type) and TCR-delta-/- mice exposed to Cl2 (400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR. RESULTS: Wild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl2 compared with TCR-delta-/- mice. Epithelial cell counts in BAL after Cl2 exposure were greater in TCR-delta-/- mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-delta-/- than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl2 exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl2 but expression was lower in TCR-delta-/- mice. CONCLUSION: The severity of airway epithelial injury after Cl2 is greater in TCR-delta-/- mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups.
Laboratory-animals; Animals; Animal-studies; Injuries; Airway-resistance; Airway-obstruction; Chlorine-compounds; Bronchial-asthma; Diseases; Dose-response; Pulmonary-system-disorders; Methacholines
Hossein Koohsari, Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Hospital du Sacre-Coeur, Montreal, Quebec