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

• Published in: Journal of allergy and clinical immunology Vol. 100; no. 4; pp. 544 - 552
• Main Authors: Redington, Anthony E., Springall, David R., Meng, Qing-Hai, Tuck a, Angela B., Holgate, Stephen T., Polak, Julia M., Howarth, Peter H.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.1997; Elsevier
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists - therapeutic use; Adult; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Biopsy; Bronchi - metabolism; Bronchi - pathology; bronchial biopsy; Chronic obstructive pulmonary disease, asthma; collagen; Collagen - metabolism; corticosteroids; endothelin; Endothelins - biosynthesis; Endothelins - immunology; Epithelium - metabolism; Female; Humans; inflammation; Male; Medical sciences; Pneumology; remodeling; PBS; endothelin; BSA; remodeling; corticosteroids; inflammation; bronchial biopsy; collagen; BAL; Asthma; ET; Human; Corticosteroid; Agonist; Endothelin; Pathophysiology; Respiratory disease; Bronchodilator; Peptide hormone; Antiinflammatory agent; Bronchus; β2-Adrenergic receptor; Chemotherapy; Treatment; Immunoreactive form; Biopsy; Vasoconstrictor agent; Obstructive pulmonary disease; Comparative study
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(97)70148-9

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 β 2-agonists, subjects with asthma treated with β 2-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 β 2-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. (J Allergy Clin Immunol 1997;100:544-52.)