Ozone inhalation induces exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice

Allergy. 2008 Apr;63(4):438-46. doi: 10.1111/j.1398-9995.2007.01587.x.


Background: Ozone (O(3)) exposure evokes asthma exacerbations by mechanisms that are poorly understood. We used a murine model to characterize the effects of O(3) 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 O(3) 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 (P(enh))], 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 P(enh) and contractile force in tracheal rings that peaked 24 h after challenge and resolved by 96 h. O(3) 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 O(3) 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: O(3) affects airway responsiveness of allergen-primed airways indirectly by increasing viability of eosinophils and eosinophil-mediated pathological changes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Allergens / immunology
  • Animals
  • Apoptosis
  • Aspergillus fumigatus / immunology
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / immunology
  • Disease Models, Animal
  • Eosinophilia / etiology
  • Eosinophilia / immunology*
  • Eosinophilia / physiopathology
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / immunology
  • Female
  • Gene Expression Regulation / drug effects
  • In Vitro Techniques
  • Inflammation / etiology
  • Inflammation / immunology*
  • Inflammation / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Oxidants, Photochemical / toxicity
  • Ozone / toxicity*
  • Trachea / drug effects
  • Trachea / physiopathology


  • Allergens
  • Cytokines
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Oxidants, Photochemical
  • Ozone
  • Ovalbumin