Ozone inhalation induces exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice
Ozone (O3) exposure evokes asthma exacerbations by mechanisms that are poorly understood. We used a murine model to characterize the effects of O3 on allergic airway inflammation and hyperresponsiveness and to identify factors that might contribute to the O3-induced exacerbation of asthma. Methods:
BALB/c mice were sensitized and challenged with Aspergillus fumigatus (Af). A group of sensitized and challenged mice was exposed to 3.0 ppm of O3 for 2 h and studied 12 h later (96 h after Af challenge). Naive mice and mice exposed to O3 alone were used as controls. Bronchoalveolar lavage (BAL) cellular and cytokine content, lung function [enhanced pause (Penh)], isometric force generation by tracheal rings and gene and protein expression of Fas and FasL were assessed. Apoptosis of eosinophils was quantified by FACS. Results:
In sensitized mice allergen challenge induced a significant increase of Penh and contractile force in tracheal rings that peaked 24 h after challenge and resolved by 96 h. O3 inhalation induced an exacerbation of airway hyperresponsiveness accompanied by recurrence of neutrophils and enhancement of eosinophils 96 h after allergen challenge. The combination of allergen and O3 exposure inhibited Fas and FasL gene and protein expression and eosinophil apoptosis and increased interleukin-5 (IL-5), granulocyte-macrophage-colony stimulating factor (GM-CSF) and G-CSF protein levels. Conclusions:
O3 affects airway responsiveness of allergen-primed airways indirectly by increasing viability of eosinophils and eosinophil-mediated pathological changes.
Document Type: Research Article
Affiliations: 1: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA 2: Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, USA 3: GlaxoSmithKline, King of Prussia, PA, USA
Publication date: April 1, 2008