Cigarette smoke differentially affects eosinophilia and remodeling in a model of house dust mite asthma.
ABSTRACT Although a similar prevalence of smoking is evident among patients with asthma and the general population, little is known about the impact of cigarette smoke on the immune inflammatory processes elicited by common environmental allergens. We investigated the impact of exposure to cigarette smoke on house dust mite (HDM)-induced allergic airway inflammation and its consequences for tissue remodeling and lung physiology in mice. BALB/c mice received intranasal HDMs daily, 5 days per week, for 3 weeks to establish chronic airway inflammation. Subsequently, mice were concurrently exposed to HDMs plus cigarette smoke, 5 days per week, for 2 weeks (HDMs + smoke). We observed significantly attenuated eosinophilia in the bronchoalveolar lavage of mice exposed to HDMs + smoke, compared with animals exposed only to HDMs. A similar activation of CD4 T cells and expression of IL-5, IL-13, and transforming growth factor-β was observed between HDM-treated and HDM + smoke-treated animals. Consistent with an effect on eosinophil trafficking, HDMs + smoke exposure attenuated the HDM-induced expression of eotaxin-1 and vascular cell adhesion molecule-1, whereas the survival of eosinophils and the numbers of blood eosinophils were not affected. Exposure to cigarette smoke also reduced the activation of B cells and the concentrations of serum IgE. Although the production of mucus decreased, collagen deposition significantly increased in animals exposed to HDMs + smoke, compared with animals exposed only to HDMs. Although airway resistance was unaffected, tissue resistance was significantly decreased in mice exposed to HDMs + smoke. Our findings demonstrate that cigarette smoke affects eosinophil migration without affecting airway resistance or modifying Th2 cell adaptive immunity in a murine model of HDM-induced asthma.
- SourceAvailable from: InTechAllergic Rhinitis, 03/2012; , ISBN: 978-953-51-0288-5
- The Journal of allergy and clinical immunology 10/2012; · 12.05 Impact Factor
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ABSTRACT: Epidemiological studies indicate that cigarette smoke (CS) exposure is a risk factor for increased sensitization and asthma development. The aim of the study was to examine the impact of CS on sensitization and allergic airway inflammation, in response to a low dose of house dust mite (HDM), and to obtain potential mechanistic insights.Mice were exposed to low doses of HDM extract combined with air or CS exposure, either during allergen sensitization or during development of allergic airway disease.Mice concomitantly exposed to low dose HDM, combined with CS for 3 weeks, demonstrated an asthmatic phenotype with significantly increased airway eosinophilia, goblet cell metaplasia, airway hyperresponsiveness and a rise in HDM-specific serum IgG1, compared to sole HDM or CS exposure. In addition, short CS inhalation, during the initial contact with HDM allergens, was sufficient to facilitate sensitization and development of a complete asthmatic phenotype after rechallenge with HDM. Mechanistically, short CS exposure amplified DC-mediated transport of FITC-labelled HDM allergens to the intrathoracic lymph nodes and generated a local Th2 response.Short CS exposure is sufficient to facilitate allergic sensitization and the development of low dose HDM-induced allergic asthma, possibly through affecting dendritic cell function.European Respiratory Journal 08/2012; · 7.13 Impact Factor