Involvement of distal airways in a chronic model of experimental asthma.
BACKGROUND
Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation.


OBJECTIVE
This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype.


METHODS
For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks.


RESULTS
In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized.


CONCLUSIONS
These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma.
Wegmann
M
M
Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps-University, Marburg, Germany.
Fehrenbach
H
H
Fehrenbach
A
A
Held
T
T
Schramm
C
C
Garn
H
H
Renz
H
H
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000648:ultrastructure; D016535:Bronchial Hyperreactivity / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000648:ultrastructure; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000485:Allergens; D016207:Cytokines; D016212:Transforming Growth Factor beta; D010047:Ovalbumin