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. 1978 Jan;19(1):287–295. doi: 10.1128/iai.19.1.287-295.1978

Morphological features and functional properties of human fibroblasts exposed to Actinomyces viscosus substances.

D Engel, H E Schroeder, R C Page
PMCID: PMC414079  PMID: 624591

Abstract

Connective tissue fibroblasts undergo cytopathic degenerative changes during certain long-term inflammatory diseases such as rheumatoid arthritis and periodontitis. The failure of inflamed tissues to repair properly may result from functional alterations of fibroblasts within the affected tissues. Numerous previous studies indicate that direct cytotoxicity by bacterial or other substances may be responsible for the cellular alterations observed in vivo. We have tested this hypothesis by exposing cultures of human diploid fibroblasts to homogenates of Actinomyces viscosus (a microorganism associated with periodontitis and capable of causing other chronic inflammatory diseases) and analyzing the effects on cell viability, morphology, and function. The cells bind and subsequently engulf relatively large quantities of the bacterial substances. These substances do not appear to be toxic to fibroblasts as determined by 51Cr release and microcytotoxicity assays, although there is a slight but significant decrease in protein synthesis (P less than 0.01) as measured by the incorporation of [14C]proline. However, collagen production was not altered, and the cytopathic alterations observed in diseased tissues in vivo did not occur in the exposed cells. These findings suggest that A. viscosus substances do not directly cause injury to connective tissue fibroblasts in periodontal disease but may, through cell-surface binding, mark these cells for subsequent immune-mediated damage.

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Selected References

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

  1. Allison A. C., Schorlemmer H. U. Activation of complement by the alternative pathway as a factor in the pathogenesis of periodontal disease. Lancet. 1976 Nov 6;2(7993):1001–1004. doi: 10.1016/s0140-6736(76)90837-0. [DOI] [PubMed] [Google Scholar]
  2. Baboolal R., Mlinek A., Powell R. N. A study of the effects of gingival plague extracts on cells cultured in vitro. J Periodontal Res. 1970;5(4):248–254. doi: 10.1111/j.1600-0765.1970.tb00724.x. [DOI] [PubMed] [Google Scholar]
  3. Berken A., Benacerraf B. Properties of antibodies cytophilic for macrophages. J Exp Med. 1966 Jan 1;123(1):119–144. doi: 10.1084/jem.123.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cordier G., Samarut C., Brochier J., Revillard J. P. Antibody-dependent cell cytoxicity (ADCC). Characterization of 'killer' cells in human lymphoid organs. Scand J Immunol. 1976;5(3):233–242. doi: 10.1111/j.1365-3083.1976.tb00274.x. [DOI] [PubMed] [Google Scholar]
  5. Courant P. R., Bader H. Bacteroides melaninogenicus and its products in the gingiva of man. Periodontics. 1966 May-Jun;4(3):131–136. [PubMed] [Google Scholar]
  6. Davies P., Fox R. I., Polyzonis M., Allison A. C., Haswell A. D. The inhibition of phagocytosis and facilitation of exocytosis in rabbit polymorphonuclear leukocytes by cytochalasin B. Lab Invest. 1973 Jan;28(1):16–22. [PubMed] [Google Scholar]
  7. Ellen R. P., Gibbons R. J. M protein-associated adherence of Streptococcus pyogenes to epithelial surfaces: prerequisite for virulence. Infect Immun. 1972 May;5(5):826–830. doi: 10.1128/iai.5.5.826-830.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Engel D., Epps D. V., Clagett J. In vivo and in vitro studies on possible pathogenic mechanisms of Actinomyces viscosus. Infect Immun. 1976 Aug;14(2):548–554. doi: 10.1128/iai.14.2.548-554.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FRASCA J. M., PARKS V. R. A ROUTINE TECHNIQUE FOR DOUBLE-STAINING ULTRATHIN SECTIONS USING URANYL AND LEAD SALTS. J Cell Biol. 1965 Apr;25:157–161. doi: 10.1083/jcb.25.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Forman J., Möller G. The effector cell in antibody-induced cell mediated immunity. Transplant Rev. 1973;17(0):108–149. doi: 10.1111/j.1600-065x.1973.tb00125.x. [DOI] [PubMed] [Google Scholar]
  11. Ghosh P., Ingman A. M., Taylor T. K. Variations in collagen, non-collagenous proteins, and hexosamine in menisci derived from osteoarthritic and rheumatoid arthritic knee joints. J Rheumatol. 1975 Mar;2(1):100–107. [PubMed] [Google Scholar]
  12. Gibbons R. J., Houte J. V. Bacterial adherence in oral microbial ecology. Annu Rev Microbiol. 1975;29:19–44. doi: 10.1146/annurev.mi.29.100175.000315. [DOI] [PubMed] [Google Scholar]
  13. Guggenheim B., Schroeder H. E. Reactions in the periodontium to continuous antigenic stimulation in sensitized gnotobiotic rats. Infect Immun. 1974 Sep;10(3):565–577. doi: 10.1128/iai.10.3.565-577.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hassell T. M., Page R. C., Narayanan A. S., Cooper C. G. Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2909–2912. doi: 10.1073/pnas.73.8.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hellström K. E., Hellström I. Cellular immunity against tumor antigens. Adv Cancer Res. 1969;12:167–223. doi: 10.1016/s0065-230x(08)60331-0. [DOI] [PubMed] [Google Scholar]
  16. Henson P. M. The adherence of leucocytes and platelets induced by fixed IgG antibody or complement. Immunology. 1969 Jan;16(1):107–121. [PMC free article] [PubMed] [Google Scholar]
  17. Irving J. T., Socransky S. S., Heeley J. D. Histological changes in experimental periodontal disease in gnotobiotic rats and conventional hamsters. J Periodontal Res. 1974;9(2):73–80. doi: 10.1111/j.1600-0765.1974.tb00656.x. [DOI] [PubMed] [Google Scholar]
  18. Ishikawa H., Ziff M. Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane. Arthritis Rheum. 1976 Jan-Feb;19(1):1–14. doi: 10.1002/art.1780190101. [DOI] [PubMed] [Google Scholar]
  19. Ivanyi L., Lehner T. Stimulation of lymphocyte transformation by bacterial antigens in patients with periodontal disease. Arch Oral Biol. 1970 Nov;15(11):1089–1096. doi: 10.1016/0003-9969(70)90121-4. [DOI] [PubMed] [Google Scholar]
  20. Jones J. M., Schwab J. H. Effects of streptococcal cell wall fragments on phagocytosis and tissue culture cells. Infect Immun. 1970 Mar;1(3):232–242. doi: 10.1128/iai.1.3.232-242.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jordan H. V., Keyes P. H., Bellack S. Periodontal lesions in hamsters and gnotobiotic rats infected with actinomyces of human origin. J Periodontal Res. 1972;7(1):21–28. doi: 10.1111/j.1600-0765.1972.tb00627.x. [DOI] [PubMed] [Google Scholar]
  22. Kobayashi I., Ziff M. Electron microscopic studies of lymphoid cells in the rheumatoid synovial membrane. Arthritis Rheum. 1973 Jul-Aug;16(4):471–486. doi: 10.1002/art.1780160407. [DOI] [PubMed] [Google Scholar]
  23. Levine M., Adams R. L., Cowley G. C. Effect of dental plaque extracts on mammalian cells in vitro. J Periodontal Res. 1973;8(5):296–303. doi: 10.1111/j.1600-0765.1973.tb01120.x. [DOI] [PubMed] [Google Scholar]
  24. Lucky A. W., Mahoney M. J., Barrnett R. J., Rosenberg L. E. Electron microscopy of human skin fibroblasts in situ during growth in culture. Exp Cell Res. 1975 May;92(2):383–393. doi: 10.1016/0014-4827(75)90392-4. [DOI] [PubMed] [Google Scholar]
  25. Mayron L. W., Loiselle R. J. Bacterial antigens and antibodies in human periodontal tissue. J Periodontol. 1973 Mar;44(3):164–166. doi: 10.1902/jop.1973.44.3.164. [DOI] [PubMed] [Google Scholar]
  26. Mlinek A., Buchner A., Hennig S., Begleiter A. Cytotoxic effects of soluble plaque extract on cells in vitro. J Periodontal Res. 1974;9(6):342–348. doi: 10.1111/j.1600-0765.1974.tb00689.x. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Perlmann P., Perlmann H., Wigzell H. Lymphocyte mediated cytotoxicity in vitro. Induction and inhibition by humoral antibody and nature of effector cells. Transplant Rev. 1972;13:91–114. doi: 10.1111/j.1600-065x.1972.tb00061.x. [DOI] [PubMed] [Google Scholar]
  30. Peter H. H., Feldman J. D. Cell-mediated cytotoxicity during rejection and enhancement of allogeneic skin grafts in rats. J Exp Med. 1972 Jun 1;135(6):1301–1315. doi: 10.1084/jem.135.6.1301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. doi: 10.1083/jcb.50.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schroeder H. E., Münzel-Pedrazzoli S., Page R. Correlated morphometric and biochemical analysis of gingival tissue in early chronic gingivitis in man. Arch Oral Biol. 1973 Jul;18(7):899–923. doi: 10.1016/0003-9969(73)90060-5. [DOI] [PubMed] [Google Scholar]
  34. Schroeder H. E., Page R. Lymphocyte-fibroblast interaction in the pathogenesis of inflammatory gingival disease. Experientia. 1972 Oct 15;28(10):1228–1230. doi: 10.1007/BF01946188. [DOI] [PubMed] [Google Scholar]
  35. Schwartz J., Stinson F. L., Parker R. B. The passage of tritiated bacterial endotoxin across intact gingival crevicular epithelium. J Periodontol. 1972 May;43(5):270–276. doi: 10.1902/jop.1972.43.5.270. [DOI] [PubMed] [Google Scholar]
  36. Simpson D. M., Avery B. E. Pathologically altered fibroblasts within lymphoid cell infiltrates in early gingivitis. J Dent Res. 1973 Sep-Oct;52(5):1156–1156. doi: 10.1177/00220345730520053301. [DOI] [PubMed] [Google Scholar]
  37. Socransky S. S., Hubersak C., Propas D. Induction of periodontal destruction in gnotobiotic rats by a human oral strain of Actinomyces naeslundii. Arch Oral Biol. 1970 Oct;15(10):993–995. doi: 10.1016/0003-9969(70)90095-6. [DOI] [PubMed] [Google Scholar]
  38. Todd F. R., 3rd Inhibition of binding between cytotoxic (T) lymphocytes and tumor target cells by inhibitors of energy metabolism. Transplantation. 1975 Oct;20(4):350–354. doi: 10.1097/00007890-197510000-00015. [DOI] [PubMed] [Google Scholar]
  39. Tolo K., Jonsen J. In vitro penetration of tritiated dextrans through rabbit oral mucosa. Arch Oral Biol. 1975 Jul;20(7):419–422. doi: 10.1016/0003-9969(75)90227-7. [DOI] [PubMed] [Google Scholar]
  40. Tsutsui M., Utsumi N., Tsubakimoto K. Cellular components of staphylococci and streptococci in inflamed human gingiva. J Dent Res. 1968 Jul-Aug;47(4):663–663. doi: 10.1177/00220345680470042501. [DOI] [PubMed] [Google Scholar]
  41. Unanue E. R., Karnovsky M. J., Engers H. D. Ligand-induced movement of lymphocyte membrane macromolecules. 3. Relationship between the formation and fate of anti-Ig-surface Ig complexes and cell metabolism. J Exp Med. 1973 Mar 1;137(3):675–689. doi: 10.1084/jem.137.3.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. White T. G., Mirikitani F. K., Hargrave P. The effect of a bacterial extract on synovial cells in tissue culture. In Vitro. 1976 Oct;12(10):702–707. doi: 10.1007/BF02797474. [DOI] [PubMed] [Google Scholar]
  43. Williams B. L., Pantalone R. M., Sherris J. C. Subgingival microflora and periodontitis. J Periodontal Res. 1976 Feb;11(1):1–18. doi: 10.1111/j.1600-0765.1976.tb00045.x. [DOI] [PubMed] [Google Scholar]
  44. Yoshida T., Cohen S., Bigazzi P. E., Kurasuji T., Amsden A. Inflammatory mediators in culture filtrates of Escherichia coli. Am J Pathol. 1975 Nov;81(2):389–400. [PMC free article] [PubMed] [Google Scholar]

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