Time course study on the development of allergen-induced airway remodeling in mice: the effect of allergen avoidance on established airway remodeling.
OBJECTIVE
We carried out a time course study on the development of allergen-induced airway remodeling in a mouse model of allergic asthma. Moreover, we examined the effect of allergen avoidance on the established airway remodeling.


METHODS
BALB/c mice were sensitized to ovalbumin (OA) with alum, and exposed daily for 3 weeks to aerosolized OA. At each designated point, bronchial responsiveness was measured, and bronchoalveolar lavage and histological examination were carried out.


RESULTS
The numbers of inflammatory leukocytes in the airways and the percentage of goblet cells in the epithelium, Th2 cytokine production, IgE production, collagen deposition beneath the basement membrane and bronchial responsiveness to acetylcholine were all markedly increased after repeated antigen challenge for 1-3 weeks. In contrast, after cessation of antigen exposure, goblet cell hyperplasia, inflammatory infiltrates and bronchial hyperresponsiveness were gradually attenuated and had almost resolved 4 weeks after cessation, but subepithelial fibrosis was still observed at this time point.


CONCLUSIONS
The present findings demonstrated that epithelial changes following repeated allergen challenge are rapidly induced and recover after the cessation of exposure, but subepithelial fibrosis has a late onset and relatively irreversible changes, and subepithelial fibrosis in contrast to goblet cells hyperplasia did not appear to contribute to bronchial hyperresponsiveness, at least, in this mouse model.
Tanaka
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Masuda
T
T
Tokuoka
S
S
Takahashi
Y
Y
Komai
M
M
Nagao
K
K
Nagai
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology; D003094:Collagen / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen; D000109:Acetylcholine