Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Sep;62(9):4005–4014. doi: 10.1128/iai.62.9.4005-4014.1994

Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections.

M S Tonetti 1, M A Imboden 1, L Gerber 1, N P Lang 1, J Laissue 1, C Mueller 1
PMCID: PMC303060  PMID: 8063420

Abstract

In bacterial infections, mononuclear and polymorphonuclear phagocytes are key components of host defenses. Recent investigations have indicated that chemokines are able to recruit and activate phagocytes. In particular, interleukin-8 (IL-8) attracts polymorphonuclear leukocytes (PMNs), while monocyte chemoattractant protein-1 (MCP-1) is selective for cells of the monocyte/macrophage lineage. In this investigation, we analyzed the in situ expression of IL-8 and MCP-1 mRNAs in human periodontal infections. Specific mRNA was detected by in situ hybridization using 35S-labeled riboprobes in frozen tissue sections. Phagocytes (PMNs and macrophages) were specifically detected as elastase-positive or CD68+ cells by a three-stage immunoperoxidase technique. Results indicated that expression of phagocyte-specific cytokines was confined to selected tissue locations and, in general, paralleled phagocyte infiltration. In particular, IL-8 expression was maximal in the junctional epithelium adjacent to the infecting microorganisms; PMN infiltration was more prominent in the same area. MCP-1 was expressed in the chronic inflammatory infiltrate and along the basal layer of the oral epithelium. Cells of the monocyte/macrophage lineage were demonstrated to be present in the same areas. The observed expression pattern may be the most economic way to establish a cell-type-selective chemotactic gradient within the tissue that is able to effectively direct polymorphonuclear phagocyte migration toward the infecting microorganisms and modulate mononuclear phagocyte infiltration in the surrounding tissues. This process may optimize host defenses and contribute to containing leukocyte infiltration to the infected and inflamed area, thus limiting tissue damage.

Full text

PDF
4005

Images in this article

4008Image
on p.4008
4010Image
on p.4010

Selected References

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

  1. Agace W. W., Hedges S. R., Ceska M., Svanborg C. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J Clin Invest. 1993 Aug;92(2):780–785. doi: 10.1172/JCI116650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birkedal-Hansen H. Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res. 1993 Nov;28(6 Pt 2):500–510. doi: 10.1111/j.1600-0765.1993.tb02113.x. [DOI] [PubMed] [Google Scholar]
  3. Birkedal-Hansen H. Role of matrix metalloproteinases in human periodontal diseases. J Periodontol. 1993 May;64(5 Suppl):474–484. doi: 10.1902/jop.1993.64.5s.474. [DOI] [PubMed] [Google Scholar]
  4. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  5. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  6. Egelberg J. The blood vessels of the dento-gingival junction. J Periodontal Res. 1966;1(3):163–179. doi: 10.1111/j.1600-0765.1966.tb01857.x. [DOI] [PubMed] [Google Scholar]
  7. Friedland J. S., Shattock R. J., Griffin G. E. Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. Cytokine. 1993 Mar;5(2):150–156. doi: 10.1016/1043-4666(93)90054-9. [DOI] [PubMed] [Google Scholar]
  8. Genco R. J. Host responses in periodontal diseases: current concepts. J Periodontol. 1992 Apr;63(4 Suppl):338–355. doi: 10.1902/jop.1992.63.4s.338. [DOI] [PubMed] [Google Scholar]
  9. Genco R. J., Van Dyke T. E., Levine M. J., Nelson R. D., Wilson M. E. 1985 Kreshover lecture. Molecular factors influencing neutrophil defects in periodontal disease. J Dent Res. 1986 Dec;65(12):1379–1391. doi: 10.1177/00220345860650120201. [DOI] [PubMed] [Google Scholar]
  10. Gillitzer R., Berger R., Mielke V., Müller C., Wolff K., Stingl G. Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ. J Invest Dermatol. 1991 Jul;97(1):73–79. doi: 10.1111/1523-1747.ep12478128. [DOI] [PubMed] [Google Scholar]
  11. Gillitzer R., Wolff K., Tong D., Müller C., Yoshimura T., Hartmann A. A., Stingl G., Berger R. MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions. J Invest Dermatol. 1993 Aug;101(2):127–131. doi: 10.1111/1523-1747.ep12363613. [DOI] [PubMed] [Google Scholar]
  12. Hanazawa S., Kawata Y., Takeshita A., Kumada H., Okithu M., Tanaka S., Yamamoto Y., Masuda T., Umemoto T., Kitano S. Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues. Infect Immun. 1993 Dec;61(12):5219–5224. doi: 10.1128/iai.61.12.5219-5224.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Held W., MacDonald H. R., Weissman I. L., Hess M. W., Mueller C. Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2239–2243. doi: 10.1073/pnas.87.6.2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  15. Hsu S. M., Soban E. Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem. 1982 Oct;30(10):1079–1082. doi: 10.1177/30.10.6182185. [DOI] [PubMed] [Google Scholar]
  16. Jiang Y., Valente A. J., Williamson M. J., Zhang L., Graves D. T. Post-translational modification of a monocyte-specific chemoattractant synthesized by glioma, osteosarcoma, and vascular smooth muscle cells. J Biol Chem. 1990 Oct 25;265(30):18318–18321. [PubMed] [Google Scholar]
  17. Kelly P. M., Bliss E., Morton J. A., Burns J., McGee J. O. Monoclonal antibody EBM/11: high cellular specificity for human macrophages. J Clin Pathol. 1988 May;41(5):510–515. doi: 10.1136/jcp.41.5.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LOE H., THEILADE E., JENSEN S. B. EXPERIMENTAL GINGIVITIS IN MAN. J Periodontol. 1965 May-Jun;36:177–187. doi: 10.1902/jop.1965.36.3.177. [DOI] [PubMed] [Google Scholar]
  19. Larsen C. G., Zachariae C. O., Oppenheim J. J., Matsushima K. Production of monocyte chemotactic and activating factor (MCAF) by human dermal fibroblasts in response to interleukin 1 or tumor necrosis factor. Biochem Biophys Res Commun. 1989 May 15;160(3):1403–1408. doi: 10.1016/s0006-291x(89)80160-3. [DOI] [PubMed] [Google Scholar]
  20. Mackenzie I. C., Gao Z. Patterns of cytokeratin expression in the epithelia of inflamed human gingiva and periodontal pockets. J Periodontal Res. 1993 Jan;28(1):49–59. doi: 10.1111/j.1600-0765.1993.tb01050.x. [DOI] [PubMed] [Google Scholar]
  21. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mazzucchelli L., Hauser C., Zgraggen K., Wagner H., Hess M., Laissue J. A., Mueller C. Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol. 1994 May;144(5):997–1007. [PMC free article] [PubMed] [Google Scholar]
  23. Moughal N. A., Adonogianaki E., Thornhill M. H., Kinane D. F. Endothelial cell leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression in gingival tissue during health and experimentally-induced gingivitis. J Periodontal Res. 1992 Nov;27(6):623–630. doi: 10.1111/j.1600-0765.1992.tb01746.x. [DOI] [PubMed] [Google Scholar]
  24. Mukaida N., Harada A., Yasumoto K., Matsushima K. Properties of pro-inflammatory cell type-specific leukocyte chemotactic cytokines, interleukin 8 (IL-8) and monocyte chemotactic and activating factor (MCAF). Microbiol Immunol. 1992;36(8):773–789. doi: 10.1111/j.1348-0421.1992.tb02080.x. [DOI] [PubMed] [Google Scholar]
  25. Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Page R. C. The role of inflammatory mediators in the pathogenesis of periodontal disease. J Periodontal Res. 1991 May;26(3 Pt 2):230–242. doi: 10.1111/j.1600-0765.1991.tb01649.x. [DOI] [PubMed] [Google Scholar]
  28. Payne J. B., Reinhardt R. A., Masada M. P., DuBois L. M., Allison A. C. Gingival crevicular fluid IL-8: correlation with local IL-1 beta levels and patient estrogen status. J Periodontal Res. 1993 Nov;28(6 Pt 1):451–453. [PubMed] [Google Scholar]
  29. Ranney R. R. Immunologic mechanisms of pathogenesis in periodontal diseases: an assessment. J Periodontal Res. 1991 May;26(3 Pt 2):243–254. doi: 10.1111/j.1600-0765.1991.tb01650.x. [DOI] [PubMed] [Google Scholar]
  30. Schmid J., Weissmann C. Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250–256. [PubMed] [Google Scholar]
  31. Schroeder H. E. Transmigration and infiltration of leucocytes in human junctional epithelium. Helv Odontol Acta. 1973 Apr;17(1):6–18. [PubMed] [Google Scholar]
  32. Schröder J. M., Christophers E. Identification of C5ades arg and an anionic neutrophil-activating peptide (ANAP) in psoriatic scales. J Invest Dermatol. 1986 Jul;87(1):53–58. doi: 10.1111/1523-1747.ep12523566. [DOI] [PubMed] [Google Scholar]
  33. Seitz M., Dewald B., Gerber N., Baggiolini M. Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. J Clin Invest. 1991 Feb;87(2):463–469. doi: 10.1172/JCI115018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Seymour G. J., Gemmell E., Reinhardt R. A., Eastcott J., Taubman M. A. Immunopathogenesis of chronic inflammatory periodontal disease: cellular and molecular mechanisms. J Periodontal Res. 1993 Nov;28(6 Pt 2):478–486. doi: 10.1111/j.1600-0765.1993.tb02108.x. [DOI] [PubMed] [Google Scholar]
  35. Socransky S. S., Haffajee A. D. The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol. 1992 Apr;63(4 Suppl):322–331. doi: 10.1902/jop.1992.63.4s.322. [DOI] [PubMed] [Google Scholar]
  36. Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
  37. Tagge D. L., O'Leary T. J., El-Kafrawy A. H. The clinical and histological response of periodontal pockets to root planing and oral hygiene. J Periodontol. 1975 Sep;46(9):527–533. doi: 10.1902/jop.1975.46.9.527. [DOI] [PubMed] [Google Scholar]
  38. Villiger P. M., Terkeltaub R., Lotz M. Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes. J Immunol. 1992 Jul 15;149(2):722–727. [PubMed] [Google Scholar]
  39. Williams R. C., Jeffcoat M. K., Howell T. H., Rolla A., Stubbs D., Teoh K. W., Reddy M. S., Goldhaber P. Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen. J Periodontol. 1989 Sep;60(9):485–490. doi: 10.1902/jop.1989.60.9.485. [DOI] [PubMed] [Google Scholar]
  40. Williams R. C., Jeffcoat M. K., Kaplan M. L., Goldhaber P., Johnson H. G., Wechter W. J. Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles. Science. 1985 Feb 8;227(4687):640–642. doi: 10.1126/science.3969553. [DOI] [PubMed] [Google Scholar]
  41. Ylä-Herttuala S., Lipton B. A., Rosenfeld M. E., Särkioja T., Yoshimura T., Leonard E. J., Witztum J. L., Steinberg D. Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5252–5256. doi: 10.1073/pnas.88.12.5252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yoshimura T., Yuhki N., Moore S. K., Appella E., Lerman M. I., Leonard E. J. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487–493. doi: 10.1016/0014-5793(89)80590-3. [DOI] [PubMed] [Google Scholar]
  43. Yu X., Antoniades H. N., Graves D. T. Expression of monocyte chemoattractant protein 1 in human inflamed gingival tissues. Infect Immun. 1993 Nov;61(11):4622–4628. doi: 10.1128/iai.61.11.4622-4628.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES