Abstract
Background: 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 O 3-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 O 3 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.
Original language | English (US) |
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Pages (from-to) | 438-446 |
Number of pages | 9 |
Journal | Allergy: European Journal of Allergy and Clinical Immunology |
Volume | 63 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2008 |
Externally published | Yes |
Keywords
- Apoptosis
- Asthma
- Eosinophils
- Murine models
- Ozone
ASJC Scopus subject areas
- Immunology