Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Nov;78(5):1150–1154. doi: 10.1172/JCI112695

Augmentation of fibroblast proliferation by bleomycin.

P L Moseley, C Hemken, G W Hunninghake
PMCID: PMC423797  PMID: 2429990

Abstract

Bleomycin-induced lung disease is characterized by fibroblast proliferation and pulmonary fibrosis. In these studies, we demonstrate that fibroblasts are relatively resistant to clinically relevant amounts (below 10(-4) U/ml) of bleomycin and that these levels of bleomycin augment fibroblast proliferation in response to various fibroblast growth factors. These observations suggest that one mechanism by which bleomycin causes pulmonary fibrosis is augmentation of fibroblast proliferation.

Full text

PDF
1153

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Absher M., Hildebran J., Trombley L., Woodcock-Mitchell J., Marsh J. Characteristics of cultured lung fibroblasts from bleomycin-treated rats. Comparisons with in vitro exposed normal fibroblasts. Am Rev Respir Dis. 1984 Jan;129(1):125–129. doi: 10.1164/arrd.1984.129.1.125. [DOI] [PubMed] [Google Scholar]
  2. Adamson I. Y., Bowden D. H. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol. 1974 Nov;77(2):185–197. [PMC free article] [PubMed] [Google Scholar]
  3. Barranco S. C., Novak J. K., Humphrey R. M. Studies on recovery from chemically induced damage in mammalian cells. Cancer Res. 1975 May;35(5):1194–1204. [PubMed] [Google Scholar]
  4. Bourne H. R., Rozengurt E. An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4555–4559. doi: 10.1073/pnas.73.12.4555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradley K. H., Kawanami O., Ferrans V. J., Crystal R. G. The fibroblast of human lung alveolar structures: a differentiated cell with a major role in lung structure and function. Methods Cell Biol. 1980;21A:37–64. doi: 10.1016/s0091-679x(08)60757-8. [DOI] [PubMed] [Google Scholar]
  6. Broughton A., Strong J. E., Holoye P. Y., Bedrossian C. W. Clinical pharmacology of bleomycin following intravenous infusion as determined by radioimmunoassay. Cancer. 1977 Dec;40(6):2772–2778. doi: 10.1002/1097-0142(197712)40:6<2772::aid-cncr2820400603>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  7. Catravas J. D., Lazo J. S., Gillis C. N. Biochemical markers of bleomycin toxicity: clearance of [14C]-5-hydroxytryptamine and [3H]norepinephrine by rabbit lung in vivo. J Pharmacol Exp Ther. 1981 May;217(2):524–529. [PubMed] [Google Scholar]
  8. Clark J. G., Kostal K. M., Marino B. A. Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production. J Clin Invest. 1983 Dec;72(6):2082–2091. doi: 10.1172/JCI111173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark J. G., Kostal K. M., Marino B. A. Modulation of collagen production following bleomycin-induced pulmonary fibrosis in hamsters. Presence of a factor in lung that increases fibroblast prostaglandin E2 and cAMP and suppresses fibroblast proliferation and collagen production. J Biol Chem. 1982 Jul 25;257(14):8098–8105. [PubMed] [Google Scholar]
  10. Collins J. F., McCullough B., Coalson J. J., Johanson W. G., Jr Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. II. Further studies on connective tissue changes. Am Rev Respir Dis. 1981 Mar;123(3):305–312. doi: 10.1164/arrd.1981.123.3.305. [DOI] [PubMed] [Google Scholar]
  11. Fahey P. J., Utell M. J., Mayewski R. J., Wandtke J. D., Hyde R. W. Early diagnosis of bleomycin pulmonary toxicity using bronchoalveolar lavage in dogs. Am Rev Respir Dis. 1982 Jul;126(1):126–130. doi: 10.1164/arrd.1982.126.1.126. [DOI] [PubMed] [Google Scholar]
  12. Giri S. N., Chen Z. L., Younker W. R., Schiedt M. J. Effects of intratracheal administration of bleomycin on GSH-shuttle enzymes, catalase, lipid peroxidation, and collagen content in the lungs of hamsters. Toxicol Appl Pharmacol. 1983 Oct;71(1):132–141. doi: 10.1016/0041-008x(83)90052-2. [DOI] [PubMed] [Google Scholar]
  13. Goldstein R. H., Lucey E. C., Franzblau C., Snider G. L. Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters. Am Rev Respir Dis. 1979 Jul;120(1):67–73. doi: 10.1164/arrd.1979.120.1.67. [DOI] [PubMed] [Google Scholar]
  14. Iqbal Z. M., Kohn K. W., Ewig R. A., Fornace A. J., Jr Single-strand scission and repair of DNA in mammalian cells by bleomycin. Cancer Res. 1976 Oct;36(10):3834–3838. [PubMed] [Google Scholar]
  15. Johnson A. R., Erdös E. G. Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase. J Clin Invest. 1977 Apr;59(4):684–695. doi: 10.1172/JCI108687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jones A. W. Bleomycin lung damage: the pathology and nature of the lesion. Br J Dis Chest. 1978 Oct;72(4):321–326. [PubMed] [Google Scholar]
  17. Korn J. H. Fibroblast prostaglandin E2 synthesis. Persistence of an abnormal phenotype after short-term exposure to mononuclear cell products. J Clin Invest. 1983 May;71(5):1240–1246. doi: 10.1172/JCI110873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mierzejewski K., Rozengurt E. Density-dependent inhibition of fibroblast growth is overcome by pure mitogenic factors. Nature. 1977 Sep 8;269(5624):155–156. doi: 10.1038/269155a0. [DOI] [PubMed] [Google Scholar]
  19. Moseley P. L., Shasby D. M., Brady M., Hunninghake G. W. Lung parenchymal injury induced by bleomycin. Am Rev Respir Dis. 1984 Dec;130(6):1082–1086. doi: 10.1164/arrd.1984.130.6.1082. [DOI] [PubMed] [Google Scholar]
  20. Povirk L. F., Hogan M., Dattagupta N. Binding of bleomycin to DNA: intercalation of the bithiazole rings. Biochemistry. 1979 Jan 9;18(1):96–101. doi: 10.1021/bi00568a015. [DOI] [PubMed] [Google Scholar]
  21. Ross R., Vogel A. The platelet-derived growth factor. Cell. 1978 Jun;14(2):203–210. doi: 10.1016/0092-8674(78)90107-1. [DOI] [PubMed] [Google Scholar]
  22. Scher C. D., Shepard R. C., Antoniades H. N., Stiles C. D. Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle. Biochim Biophys Acta. 1979 Aug 10;560(2):217–241. doi: 10.1016/0304-419x(79)90020-9. [DOI] [PubMed] [Google Scholar]
  23. Takeshita M., Grollman A. P., Ohtsubo E., Ohtsubo H. Interaction of bleomycin with DNA. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5983–5987. doi: 10.1073/pnas.75.12.5983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thrall R. S., McCormick J. R., Jack R. M., McReynolds R. A., Ward P. A. Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin. Am J Pathol. 1979 Apr;95(1):117–130. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES