Ozone inhalation induces exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice.
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.
Kierstein
S
S
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3403, USA.
Krytska
K
K
Sharma
S
S
Amrani
Y
Y
Salmon
M
M
Panettieri
R A
RA
Zangrilli
J
J
Haczku
A
A
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D001232:Aspergillus fumigatus / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010083:Oxidants, Photochemical / Q000633:toxicity; D010126:Ozone / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
D000485:Allergens; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D010083:Oxidants, Photochemical; D010126:Ozone; D010047:Ovalbumin