AD Cambrey, NK Harrison, KE Dawes, AM Southcott, CM Black, RM du Bois, GJ Laurent and RJ McAnulty
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.

Pulmonary fibrosis is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). The pathogenesis of this condition is poorly understood, but one of the earliest pathologic features is endothelial and epithelial cell injury with subsequent regeneration. Endothelial and epithelial cells can release several mediators, including endothelin-1 (ET-1). In this study, we investigated the levels of ET-1 in bronchoalveolar lavage fluid (BALF) from patients with SSc and assessed the contribution of ET-1 to the fibroblast mitogenic activity induced by these fluids. A total of 26 patients were evaluated and divided into those with evidence of pulmonary fibrosis, assessed by thin-section computed tomography (group I, n = 16), and those with a normal scan (group II, n = 10). BALF from both groups of patients stimulated fibroblast proliferation. Values expressed as median (range) percentage increase above media controls were 25.5% (5.0 to 47.8%) and 27.6% (10.9 to 51.6%) for groups I and II, respectively (P < 0.02 in both cases). Mitogenic activity was inhibited by about 40% in the presence of either a neutralizing antibody to ET-1 or two synthetic ET-1 receptor ligands. Levels of ET-1 in BALF, expressed as medians (range) were 2.90 ng/mg albumin (0.68 to 5.75) in patients with SSc and 1.23 ng/mg albumin (0.84 to 2.0) in control patients (P < 0.02). Furthermore, ET-1 levels in BALF from patients in group II (3.83 ng/mg albumin, range 1.76 to 5.75) were elevated compared with those in group I (2.62 ng/mg albumin, range 0.68 to 3.81; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				R. M. du Bois Blocking endothelin: breaking new ground Eur. Respir. Rev., August 1, 2007; 16(102): 24 - 29. [Abstract] [Full Text] [PDF]

				R. Jain, P. W. Shaul, Z. Borok, and B. C. Willis Endothelin-1 Induces Alveolar Epithelial-Mesenchymal Transition through Endothelin Type A Receptor-Mediated Production of TGF-beta1 Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 38 - 47. [Abstract] [Full Text] [PDF]

				N. H.S. Kim and L. J. Rubin Endothelin in Health and Disease: Endothelin Receptor Antagonists in the Management of Pulmonary Artery Hypertension Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 9 - 19. [Abstract] [PDF]

				R. P. MARSHALL, G. BELLINGAN, S. WEBB, A. PUDDICOMBE, N. GOLDSACK, R. J. MCANULTY, and G. J. LAURENT Fibroproliferation Occurs Early in the Acute Respiratory Distress Syndrome and Impacts on Outcome Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1783 - 1788. [Abstract] [Full Text]

				Y. Li, M. Rahmanian, C. Widström, G. Lepperdinger, G. I. Frost, and P. Heldin Irradiation-Induced Expression of Hyaluronan (HA) Synthase 2 and Hyaluronidase 2 Genes in Rat Lung Tissue Accompanies Active Turnover of HA and Induction of Types I and III Collagen Gene Expression Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 411 - 418. [Abstract] [Full Text]

				P. Teder and P. W. Noble A Cytokine Reborn? . Endothelin-1 in Pulmonary Inflammation and Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2000; 23(1): 7 - 10. [Full Text]

				B. Hocher, A. Schwarz, K. A. Fagan, C. Thöne-Reineke, K. El-Hag, H. Kusserow, S. Elitok, C. Bauer, H.-H. Neumayer, D. M. Rodman, et al. Pulmonary Fibrosis and Chronic Lung Inflammation in ET-1 Transgenic Mice Am. J. Respir. Cell Mol. Biol., July 1, 2000; 23(1): 19 - 26. [Abstract] [Full Text]

				D. J. Abraham, X. Shiwen, C. M. Black, S. Sa, Y. Xu, and A. Leask Tumor Necrosis Factor alpha Suppresses the Induction of Connective Tissue Growth Factor by Transforming Growth Factor-beta in Normal and Scleroderma Fibroblasts J. Biol. Chem., May 12, 2000; 275(20): 15220 - 15225. [Abstract] [Full Text] [PDF]

				L. Bouthillier, R. Vincent, P. Goegan, I. Y. R. Adamson, S. Bjarnason, M. Stewart, J. Guenette, M. Potvin, and P. Kumarathasan Acute Effects of Inhaled Urban Particles and Ozone : Lung Morphology, Macrophage Activity, and Plasma Endothelin-1 Am. J. Pathol., December 1, 1998; 153(6): 1873 - 1884. [Abstract] [Full Text] [PDF]

				S. E. Mutsaers, M. L. Foster, R. C. Chambers, G. J. Laurent, and R. J. McAnulty Increased Endothelin-1 and Its Localization during the Development of Bleomycin-induced Pulmonary Fibrosis in Rats Am. J. Respir. Cell Mol. Biol., May 1, 1998; 18(5): 611 - 619. [Abstract] [Full Text]

				C. ODOUX, B. CRESTANI, G. LEBRUN, C. ROLLAND, P. AUBIN, N. SETA, M.-F. KAHN, J. FIET, and M. AUBIER Endothelin-1 Secretion by Alveolar Macrophages in Systemic Sclerosis Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1429 - 1435. [Abstract] [Full Text]