Immunoreactive endothelin in bronchial biopsy specimens: increased expression in asthma and modulation by corticosteroid therapy.

BACKGROUND

The human endothelin (ET) family comprises three 21-amino-acid peptides, which are potent bronchoconstrictors and have a number of other biologic properties relevant to the pathophysiology of asthma.

OBJECTIVE

We sought to compare the expression of immunoreactive ET in bronchial biopsy specimens from subjects with asthma treated only with inhaled beta2-agonists, subjects with asthma treated with beta2-agonists and corticosteroids, and control subjects without asthma.

METHODS

Biopsy specimens were obtained by fiberoptic bronchoscopy and stained immunohistochemically with a specific ET antiserum. Epithelial ET expression was quantitated by using a computer-assisted system of image analysis. Numbers of inflammatory cells and depth of subepithelial collagen deposition were also determined.

RESULTS

Immunoreactive ET was principally localized in the airway epithelium. The proportion of epithelium immunostained was significantly increased in the subjects with asthma not treated with steroids (35.4% +/- 3.8%) compared with that of both the control subjects (16.2% +/- 1.9%, p < 0.0001) and the subjects with asthma treated with steroids (14.3% +/- 2.0%, p < 0.0001). The last two groups did not differ significantly from one another. There were no significant correlations between ET expression and either physiologic parameters or indexes of airway inflammation and remodeling.

CONCLUSION

Bronchial epithelial expression of immunoreactive ET is increased in subjects with asthma receiving treatment only with beta2-agonists but not in subjects with asthma also receiving corticosteroid therapy. These findings are consistent with the hypothesis that ET is implicated in the pathophysiology of asthma.