Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1982 Dec;38(3):986–992. doi: 10.1128/iai.38.3.986-992.1982

Inhibition of fibroblast proliferation by Actinobacillus actinomycetemcomitans.

B J Shenker, M E Kushner, C C Tsai
PMCID: PMC347847  PMID: 7152684

Abstract

We have examined soluble sonic extracts of Actinobacillus actinomycetemcomitans for their ability to alter human and murine fibroblast proliferation. We found that extracts of all A. actinomycetemcomitans strains examined (both leukotoxic and nonleukotoxic) caused a dose-dependent inhibition of both murine and human fibroblast proliferation as assessed by DNA synthesis ([3H]thymidine incorporation). Addition of sonic extract simultaneously with [3H]thymidine had no effect on incorporation, indicating that suppression was not due to the presence of excessive amounts of cold thymidine. Inhibition of DNA synthesis was also paralleled by decreased RNA synthesis ([3H]uridine incorporation) and by a decrease in cell growth as assessed by direct cell counts; there was no effect on cell viability. The suppressive factor(s) is heat labile; preliminary purification and characterization studies indicate that it is a distinct and separate moiety from other A. actinomycetemcomitans mediators previously reported, including leukotoxin, immune suppressive factor, and endotoxin. Although it is not clear how A. actinomycetemcomitans acts to cause disease, we propose that one aspect of the pathogenicity of this organism rests in its ability to inhibit fibroblast growth, which in turn could contribute to the collagen loss associated with certain forms of periodontal disease, in particular juvenile periodontitis.

Full text

PDF
988

Selected References

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

  1. Alexander J. W., Bossert J. E., McClellan M. A., Altemeier W. A. Stimulants of cellular proliferation in wounds. Arch Surg. 1971 Aug;103(2):167–174. doi: 10.1001/archsurg.1971.01350080083012. [DOI] [PubMed] [Google Scholar]
  2. Baehni P., Tsai C. C., McArthur W. P., Hammond B. F., Taichman N. S. Interaction of inflammatory cells and oral microorganisms. VIII. Detection of leukotoxic activity of a plaque-derived gram-negative microorganism. Infect Immun. 1979 Apr;24(1):233–243. doi: 10.1128/iai.24.1.233-243.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Castor C. W., Yaron M. Leukocyte-connective tissue cell interaction. II. The specificity, duration, and mechanism of interaction effects. Arthritis Rheum. 1969 Aug;12(4):374–386. doi: 10.1002/art.1780120405. [DOI] [PubMed] [Google Scholar]
  4. Golub L. M., Siegel K., Ramamurthy N. S., Mandel I. D. Some characteristics of collagenase activity in gingival crevicular fluid and its relationship to gingival diseases in humans. J Dent Res. 1976 Nov-Dec;55(6):1049–1057. doi: 10.1177/00220345760550060701. [DOI] [PubMed] [Google Scholar]
  5. Higerd T. B., Vesole D. H., Goust J. M. Inhibitory effects of extracellular products from oral bacteria on human fibroblasts and stimulated lymphocytes. Infect Immun. 1978 Aug;21(2):567–574. doi: 10.1128/iai.21.2.567-574.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jimenez S. A., McArthur W., Rosenbloom J. Inhibition of collagen synthesis by mononuclear cell supernates. J Exp Med. 1979 Dec 1;150(6):1421–1431. doi: 10.1084/jem.150.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kiley P., Holt S. C. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun. 1980 Dec;30(3):862–873. doi: 10.1128/iai.30.3.862-873.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Manson J. D., Lehner T. Clinical features of juvenile periodontitis (periodontosis). J Periodontol. 1974 Aug;45(8):636–640. doi: 10.1902/jop.1974.45.8.2.636. [DOI] [PubMed] [Google Scholar]
  9. Narayanan A. S., Page R. C. Biochemical characterization of collagens synthesized by fibroblasts derived from normal and diseased human gingiva. J Biol Chem. 1976 Sep 25;251(18):5464–5471. [PubMed] [Google Scholar]
  10. Newman M. G., Socransky S. S. Predominant cultivable microbiota in periodontosis. J Periodontal Res. 1977 Mar;12(2):120–128. doi: 10.1111/j.1600-0765.1977.tb00114.x. [DOI] [PubMed] [Google Scholar]
  11. Page R. C., Schroeder H. E. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976 Mar;34(3):235–249. [PubMed] [Google Scholar]
  12. Saxén L. Juvenile periodontitis. J Clin Periodontol. 1980 Feb;7(1):1–19. doi: 10.1111/j.1600-051x.1980.tb01944.x. [DOI] [PubMed] [Google Scholar]
  13. Schmidt J. A., Mizel S. B., Cohen D., Green I. Interleukin 1, a potential regulator of fibroblast proliferation. J Immunol. 1982 May;128(5):2177–2182. [PubMed] [Google Scholar]
  14. Shenker B. J., McArthur W. P., Tsai C. C. Immune suppression induced by Actinobacillus actinomycetemcomitans. I. Effects on human peripheral blood lymphocyte responses to mitogens and antigens. J Immunol. 1982 Jan;128(1):148–154. [PubMed] [Google Scholar]
  15. Stevens R. H., Sela M. N., Shapira J., Hammond B. F. Detection of a fibroblast proliferation inhibitory factor from Capnocytophaga sputigena. Infect Immun. 1980 Jan;27(1):271–275. doi: 10.1128/iai.27.1.271-275.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tanner A. C., Haffer C., Bratthall G. T., Visconti R. A., Socransky S. S. A study of the bacteria associated with advancing periodontitis in man. J Clin Periodontol. 1979 Oct;6(5):278–307. doi: 10.1111/j.1600-051x.1979.tb01931.x. [DOI] [PubMed] [Google Scholar]
  17. Tsai C. C., McArthur W. P., Baehni P. C., Hammond B. F., Taichman N. S. Extraction and partial characterization of a leukotoxin from a plaque-derived Gram-negative microorganism. Infect Immun. 1979 Jul;25(1):427–439. doi: 10.1128/iai.25.1.427-439.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wahl L. M., Wahl S. M., Mergenhagen S. E., Martin G. R. Collagenase production by endotoxin-activated macrophages. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3598–3601. doi: 10.1073/pnas.71.9.3598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wahl S. M., Wahl L. M., McCarthy J. B. Lymphocyte-mediated activation of fibroblast proliferation and collagen production. J Immunol. 1978 Sep;121(3):942–946. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES