title: 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.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Botelho
authors.forename: Alba
authors.initials: A
authors.lastname: Llop-Guevara
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Trimble
authors.forename: Jake K
authors.initials: JK
authors.lastname: Nikota
authors.forename: Carla M T
authors.initials: CM
authors.lastname: Bauer
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Lambert
authors.forename: Sussan
authors.initials: S
authors.lastname: Kianpour
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D056151:Airway Remodeling; D000403:Airway Resistance; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001402:B-Lymphocytes / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D054413:Chemokine CCL11 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D039981:Pyroglyphidae / Q000276:immunology*; D012907:Smoking / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018793:Interleukin-13; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1