title: Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis.
abstract: 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.
authors.affiliation: Department of Pathology, Montreal General Hospital, McGill University, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Giaid
authors.forename: R P
authors.initials: RP
authors.lastname: Michel
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Sheppard
authors.forename: B
authors.initials: B
authors.lastname: Corrin
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D015415:Biomarkers; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D015415:Biomarkers; D016232:Endothelins; D012333:RNA, Messenger