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

Lancet. 1993 Jun 19;341(8860):1550-4. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Biomarkers
  • Endothelins
  • RNA, Messenger