Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis

• Published in: The Lancet (British edition) Vol. 341; no. 8860; p. 1550
• Main Authors: Giaid, A, Michel, R P, Stewart, D J, Sheppard, M, Corrin, B, Hamid, Q
• Format: Journal Article
• Language: English
• Published: England 19-06-1993
• Subjects: Biomarkers; Endothelins - biosynthesis; Endothelium, Vascular - metabolism; Epithelium - metabolism; Female; Humans; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Immunohistochemistry; In Situ Hybridization; Lung - blood supply; Lung - metabolism; Male; Middle Aged; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - physiopathology; RNA, Messenger - analysis
• ISSN: 0140-6736
• DOI: 10.1016/0140-6736(93)90694-C

The vasoconstrictor and mitogenic peptide endothelin-1 (ET-1) is believed to play a part in fibrosis and collagen production. We examined expression of ET-1 in lung tissue from 52 patients with interstitial lung fibrosis, of whom 45 had cryptogenic fibrosing alveolitis (CFA), 10 had CFA and concomitant pulmonary hypertension, and 7 had non-specific focal fibrosis. 17 normal unused donor lungs were studied as controls. Immunohistochemistry and in-situ hybridisation were done with polyclonal antisera to ET-1 and its precursor big ET-1, and complementary RNA probes for preproET-1. Normal lung tissue and that from patients with focal fibrosis expressed very little ET-1. By contrast, there was striking expression of ET-1 in lung tissue from patients with CFA. Immunostains for ET-1 and big ET-1 and expression of ET-1 mRNA were most prominent in airway epithelium and type II pneumocytes, particularly those lining areas of young granulation tissue. ET-1-like immunoreactivity and mRNA were also present in pulmonary vascular endothelial cells, particularly in specimens from patients with pulmonary hypertension. In all patients, there was a significant correlation between ET-1-like immunoreactivity and histological parameters of disease activity (r = 0.78, 95% CI 0.65-0.87, p < 0.001). These findings suggest a possible role for cell-specific expression of ET-1 in the pathogenesis of CFA and associated pulmonary hypertension.