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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1995 Apr;48(4):330–334. doi: 10.1136/jcp.48.4.330

Endothelin-1 in idiopathic pulmonary fibrosis.

M Uguccioni 1, L Pulsatelli 1, B Grigolo 1, A Facchini 1, L Fasano 1, C Cinti 1, M Fabbri 1, G Gasbarrini 1, R Meliconi 1
PMCID: PMC502551  PMID: 7615852

Abstract

AIMS--To evaluate whether endothelin-1 is involved in the pathology of idiopathic pulmonary fibrosis (IPF). METHODS--Plasma endothelin-1 concentrations were evaluated in 37 patients with IPF and 27 normal controls by radioimmunoassay. In addition, expression of endothelin-1 in lung tissue was evaluated in biopsy specimens obtained from four patients with IPF. Three biopsy specimens of normal lung were used as controls. Endothelin-1 immunoreactivity was detected using immunohistochemistry. RESULTS--Elevated endothelin-1 plasma concentrations were found in patients with IPF compared with controls and a positive correlation was found with duration of disease. No significant difference was observed between treated and untreated patients with IPF. Increased endothelin-1 immunoreactivity was found in lungs of three of four patients with IPF. Endothelin-1 positive consisted mainly of small vessel endothelial cells. Some scattered macrophages were also positive. CONCLUSIONS--Elevated plasma concentrations and expression of endothelin-1 in lung tissue are suggestive of increased production of endothelin-1 in at least a proportion of patients with IPF. Consequently, endothelin-1 activity could play a role in the fibrogenic process of the disease.

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Selected References

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  1. Broekelmann T. J., Limper A. H., Colby T. V., McDonald J. A. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6642–6646. doi: 10.1073/pnas.88.15.6642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Giaid A., Gibson S. J., Herrero M. T., Gentleman S., Legon S., Yanagisawa M., Masaki T., Ibrahim N. B., Roberts G. W., Rossi M. L. Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain. Histochemistry. 1991;95(3):303–314. doi: 10.1007/BF00266781. [DOI] [PubMed] [Google Scholar]
  3. Giaid A., Gibson S. J., Ibrahim B. N., Legon S., Bloom S. R., Yanagisawa M., Masaki T., Varndell I. M., Polak J. M. Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7634–7638. doi: 10.1073/pnas.86.19.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Giaid A., Michel R. P., Stewart D. J., Sheppard M., Corrin B., Hamid Q. Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis. Lancet. 1993 Jun 19;341(8860):1550–1554. doi: 10.1016/0140-6736(93)90694-c. [DOI] [PubMed] [Google Scholar]
  5. Giaid A., Yanagisawa M., Langleben D., Michel R. P., Levy R., Shennib H., Kimura S., Masaki T., Duguid W. P., Stewart D. J. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993 Jun 17;328(24):1732–1739. doi: 10.1056/NEJM199306173282402. [DOI] [PubMed] [Google Scholar]
  6. Haynes W. G., Webb D. J. The endothelin family of peptides: local hormones with diverse roles in health and disease? Clin Sci (Lond) 1993 May;84(5):485–500. doi: 10.1042/cs0840485. [DOI] [PubMed] [Google Scholar]
  7. Hirata Y., Takagi Y., Fukuda Y., Marumo F. Endothelin is a potent mitogen for rat vascular smooth muscle cells. Atherosclerosis. 1989 Aug;78(2-3):225–228. doi: 10.1016/0021-9150(89)90227-x. [DOI] [PubMed] [Google Scholar]
  8. Hyde D. M., King T. E., Jr, McDermott T., Waldron J. A., Jr, Colby T. V., Thurlbeck W. M., Flint W. M., Ackerson L., Cherniack R. M. Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system. Am Rev Respir Dis. 1992 Oct;146(4):1042–1047. doi: 10.1164/ajrccm/146.4.1042. [DOI] [PubMed] [Google Scholar]
  9. Inagaki H., Bishop A. E., Escrig C., Wharton J., Allen-Mersh T. G., Polak J. M. Localization of endothelinlike immunoreactivity and endothelin binding sites in human colon. Gastroenterology. 1991 Jul;101(1):47–54. doi: 10.1016/0016-5085(91)90458-w. [DOI] [PubMed] [Google Scholar]
  10. Kahaleh M. B. Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action. Arthritis Rheum. 1991 Aug;34(8):978–983. doi: 10.1002/art.1780340807. [DOI] [PubMed] [Google Scholar]
  11. Kourembanas S., Marsden P. A., McQuillan L. P., Faller D. V. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest. 1991 Sep;88(3):1054–1057. doi: 10.1172/JCI115367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kurihara H., Yoshizumi M., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Hamaoki M., Kato H., Yazaki Y. Transforming growth factor-beta stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1435–1440. doi: 10.1016/0006-291x(89)92270-5. [DOI] [PubMed] [Google Scholar]
  13. Kusuhara M., Yamaguchi K., Ohnishi A., Abe K., Kimura S., Oono H., Hori S., Nakamura Y. Endothelin potentiates growth factor-stimulated DNA synthesis in Swiss 3T3 cells. Jpn J Cancer Res. 1989 Apr;80(4):302–305. doi: 10.1111/j.1349-7006.1989.tb02310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meliconi R., Lalli E., Borzì R. M., Sturani C., Galavotti V., Gunella G., Miniero R., Facchini A., Gasbarrini G. Idiopathic pulmonary fibrosis: can cell mediated immunity markers predict clinical outcome? Thorax. 1990 Jul;45(7):536–540. doi: 10.1136/thx.45.7.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miyasaka N., Hirata Y., Ando K., Sato K., Morita H., Shichiri M., Kanno K., Tomita K., Marumo F. Increased production of endothelin-1 in patients with inflammatory arthritides. Arthritis Rheum. 1992 Apr;35(4):397–400. doi: 10.1002/art.1780350406. [DOI] [PubMed] [Google Scholar]
  16. Murch S. H., Braegger C. P., Sessa W. C., MacDonald T. T. High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis. Lancet. 1992 Feb 15;339(8790):381–385. doi: 10.1016/0140-6736(92)90077-g. [DOI] [PubMed] [Google Scholar]
  17. Nakaki T., Nakayama M., Yamamoto S., Kato R. Endothelin-mediated stimulation of DNA synthesis in vascular smooth muscle cells. Biochem Biophys Res Commun. 1989 Feb 15;158(3):880–883. doi: 10.1016/0006-291x(89)92804-0. [DOI] [PubMed] [Google Scholar]
  18. Nosal A., Schleissner L. A., Mishkin F. S., Lieberman J. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Ann Intern Med. 1979 Mar;90(3):328–331. doi: 10.7326/0003-4819-90-3-328. [DOI] [PubMed] [Google Scholar]
  19. Shaw R. J., Benedict S. H., Clark R. A., King T. E., Jr Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF(B) gene activation and up-regulation by interferon gamma. Am Rev Respir Dis. 1991 Jan;143(1):167–173. doi: 10.1164/ajrccm/143.1.167. [DOI] [PubMed] [Google Scholar]
  20. Stewart D. J., Levy R. D., Cernacek P., Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med. 1991 Mar 15;114(6):464–469. doi: 10.7326/0003-4819-114-6-464. [DOI] [PubMed] [Google Scholar]
  21. Watters L. C., King T. E., Schwarz M. I., Waldron J. A., Stanford R. E., Cherniack R. M. A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1986 Jan;133(1):97–103. doi: 10.1164/arrd.1986.133.1.97. [DOI] [PubMed] [Google Scholar]
  22. Yamane K., Miyauchi T., Suzuki N., Yuhara T., Akama T., Suzuki H., Kashiwagi H. Significance of plasma endothelin-1 levels in patients with systemic sclerosis. J Rheumatol. 1992 Oct;19(10):1566–1571. [PubMed] [Google Scholar]
  23. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  24. Yoshimoto S., Ishizaki Y., Sasaki T., Murota S. Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells. Stroke. 1991 Mar;22(3):378–383. doi: 10.1161/01.str.22.3.378. [DOI] [PubMed] [Google Scholar]
  25. Yoshizumi M., Kurihara H., Morita T., Yamashita T., Oh-hashi Y., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Interleukin 1 increases the production of endothelin-1 by cultured endothelial cells. Biochem Biophys Res Commun. 1990 Jan 15;166(1):324–329. doi: 10.1016/0006-291x(90)91948-r. [DOI] [PubMed] [Google Scholar]

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