Enhanced osteopontin expression in a murine model of allergen-induced airway remodelling.
BACKGROUND
Airway remodelling is a central pathophysiological feature of chronic asthma. A wide variety of cytokines and growth factors are likely to be involved in the development of airway remodelling. Osteopontin (OPN) is a cytokine with pro-fibrotic properties; however, its role in airway remodelling in asthma has not been explored.


OBJECTIVE
To determine the expression and cellular sources of OPN in a murine model of chronic allergen-induced airway remodelling.


METHODS
BALB/c mice were sensitized and exposed to ovalbumin (OVA) or saline inhalations for 5 weeks and killed 24 h after the last inhalation. The following parameters of inflammation and remodelling were assessed: differential cell counts in bronchoalveolar lavage (BAL) fluid lung collagen content (colorimetric biochemical assay) and peribronchial smooth muscle content (immunohistochemistry, followed by image analysis). OPN expression in BAL and lung tissue was determined by PCR and ELISA. The cellular source and distribution of OPN were evaluated by immunohistochemistry and immunofluorescence.


RESULTS
OPN expression is up-regulated in lung tissue and in BAL fluid of OVA-treated mice and correlates with collagen content and peribronchial smooth muscle area. In addition, OPN significantly increases collagen deposition in vitro in a murine lung cell line. Cells producing OPN include the airway epithelium and cells of the submucosal inflammatory infiltrate (T cells, eosinophils, and macrophages). Positive staining for OPN was also observed in bronchial tissue from human asthmatic subjects.


CONCLUSIONS
OPN expression in the lungs is increased in a murine model of allergen-induced chronic airway remodelling, suggesting a role for this cytokine in airway remodelling in asthma.
Kohan
M
M
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Bader
R
R
Puxeddu
I
I
Levi-Schaffer
F
F
Breuer
R
R
Berkman
N
N
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053495:Osteopontin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D053495:Osteopontin; D010047:Ovalbumin