Chemokines in human periodontal disease tissues

Immunopathology Laboratory, Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia

Correspondence: E Gemmell, Immunopathology Laboratory, Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane 4072, Australia. E-mail: ua.ude.qu.xobliam@llemmeg.e

Immunopathology Laboratory, Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia

Accepted 2001 Jan 12.

Abstract

An immunoperoxidase technique was used to examine IP-10 (interferon-gamma inducible protein 10), RANTES (regulated on activation normal T cell expressed and secreted), MCP-1 (monocyte chemoattractant protein-1), and MIP-1alpha (macrophage inflammatory protein-1alpha) in gingival biopsies from 21 healthy/gingivitis and 26 periodontitis subjects. The samples were placed into 3 groups according to the size of infiltrate. MIP-1alpha+ cells were more abundant than the other chemokines with few MCP-1+ cells. The mean percent MIP-1alpha+ cells was higher than the percent MCP-1+ cells (P = 0·02) in group 2 (intermediate size infiltrates) lesions from periodontitis subjects, other differences not being significant due to the large variations between tissue samples. Analysis of positive cells in relation to CD4/CD8 ratios showed that with an increased proportion of CD8+ cells, the mean percent MIP-1alpha+ cells was significantly higher in comparison with the mean percent RANTES+ and MCP-1+ cells (P < 0·015). Endothelial cells were MCP-1+ although positive capillaries were found on the periphery of infiltrates only. Keratinocyte expression of chemokines was weak and while the numbers of healthy/gingivitis and periodontitis tissue sections positive for IP-10, RANTES and MCP-1 reduced with increasing inflammation, those positive for MIP-1alpha remained constant for all groups. In conclusion, fewer leucocytes expressed MCP-1 in gingival tissue sections, however, the percent MIP-1alpha+ cells was increased particularly in tissues with increased proportions of CD8 cells and B cells with increasing inflammation and also in tissues with higher numbers of macrophages with little inflammation. Further studies are required to determine the significance of MIP-1alpha in periodontal disease.

Keywords: chemokines, periodontal disease, antigen presenting cells, lymphocytes

Abstract

H/G, healthy/gingivitis; AP, adult periodontitis

Group 1, small infiltrates

Group 2, intermediate infiltrates

Group 3, extensive infiltrates

Acknowledgments

This work was supported by the Government Employees Medical Research Fund and the Australian Dental Research Fund Incorporated.

Acknowledgments

References

1. Seymour GJPossible mechanisms involved in the immunoregulation of chronic inflammatory periodontal disease. J Dent Res. 1987;66:2–9.[PubMed][Google Scholar]
2. Kornman KS, Page RC, Tonetti MSThe host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000. 1997;14:33–53.[PubMed][Google Scholar]
3. Seymour GJ, Greenspan JSThe phenotypic characterization of lymphocyte subpopulations in established human periodontal disease. J Periodontal Res. 1979;14:39–46.[PubMed][Google Scholar]
4. Zappa U, Reinking-Zappa M, Graf H, Espeland MCell populations and episodic periodontal attachment loss in humans. J Clin Periodontol. 1991;18:508–15.[PubMed][Google Scholar]
5. Zappa U, Reinking-Zappa M, Graf H, Case DCell populations associated with active probing attachment loss. J Periodontol. 1992;63:748–52.[PubMed][Google Scholar]
6. Baggiolini M, Dewald B, MoSeries BHuman chemokines: an update. Annu Rev Immunol. 1997;15:675–705.[PubMed][Google Scholar]
7. Gemmell E, Grieco DA, Seymour GJChemokine expression in Porphyromonas gingivalis-specific T-cell lines. Oral Microbiol Immunol. 2000;15:166–71.[PubMed][Google Scholar]
8. Bird PS, Gemmell E, Polak B, Paton RG, Sosroseno W, Seymour GJProtective immunity to Porphyromonas gingivalis infection in a murine model. J Periodontol. 1995;66:351–62.[PubMed][Google Scholar]
9. Gemmell E, Seymour GJCytokine profiles of cells extracted from humans with periodontal diseases. J Dent Res. 1998;77:16–26.[PubMed][Google Scholar]
10. Siveke JT, Hamann AT helper 1 and T helper 2 cells respond differentially to chemokines. J Immunol. 1998;160:550–4.[PubMed][Google Scholar]
11. Gemmell E, Walsh LJ, Savage NW, Seymour GJAdhesion molecule expression in chronic inflammatory periodontal disease tissue. J Periodontal Res. 1994;29:46–53.[PubMed][Google Scholar]
12. Haapasalmi K, Makela M, Oksala O, Heino J, Yamada KM, Uitto VJ, Larjava HExpression of epithelial adhesion proteins and integrins in chronic inflammation. Am J Pathol. 1995;147:193–206.[Google Scholar]
13. Suchett-Kaye G, Morrier JJ, Barsotti OInteractions between non-immune host cells and the immune system during periodontal disease: role of the gingival keratinocyte. Crit Rev Oral Biol Med. 1998;9:292–305.[PubMed][Google Scholar]
14. Seymour GJ, Powell RN, Aitken JF. Experimental gingivitis in humans. A clinical and histologic investigation. J Periodontol. 1983;54:522–8.[PubMed]
15. Seymour GJ, Gemmell E, Walsh LJ, Powell RNImmunohistological analysis of experimental gingivitis in humans. Clin Exp Immunol. 1988;71:132–7.[Google Scholar]
16. Gemmell E, Seymour GJGamma delta T lymphocytes in human periodontal disease tissue. J Periodontol. 1995;66:780–5.[PubMed][Google Scholar]
17. Poulter LW, Chilosi M, Seymour GJ, Hobbs S, Janossy G. Immunofluorescence membrane staining and cytochemistry, applied in combination for analyzing cell interactions in situ. In: Polak J, van Noorden S, editors. Immunocytochemistry Practical Applications in Pathology and Biology. Bristol: Wright; 1983. pp. 233–4. [PubMed]
18. Gemmell E, Bird PS, Bowman JJD, Xu L, Polak B, Walsh LJ, Seymour GJImmunohistological study of lesions induced by Porphyromonas gingivalis in a murine model. Oral Microbiol Immunol. 1997;12:288–97.[PubMed][Google Scholar]
19. Reinhardt RA, Bolton RW, McDonald TL, DuBois LM, Kaldahl WBIn situ lymphocyte subpopulations from active versus stable periodontal sites. J Periodontol. 1988;59:656–70.[PubMed][Google Scholar]
20. Moll HThe role of chemokines and accessory cells in the immunoregulation of cutaneous leishmaniasis. Behring Inst Mitt. 1997;99:73–8.[PubMed][Google Scholar]
21. Chapple CC, Srivastava M, Hunter NFailure of macrophage activation in destructive periodontal disease. J Pathol. 1998;186:281–6.[PubMed][Google Scholar]
22. Reife RA, Shapiro RA, Bamber BA, Berry KK, Mick GE, Darveau RP. Porphyromonas gingivalis lipopolysaccharide is poorly recognized by molecular components of innate host defense in a mouse model of early inflammation. Infect Immun. 1995;63:4686–94.
23. Yu X, Antoniades HN, Graves DTExpression of monocyte chemoattractant protein 1 in human inflamed gingival tissues. Infect Immun. 1993;61:4622–8.[Google Scholar]
24. Yu X, Barnhill RL, Graves DTExpression of monocyte chemoattractant protein-1 in delayed type hypersensitivity reactions in the skin. Lab Invest. 1994;71:226–35.[PubMed][Google Scholar]
25. Mustafa T, Phyu S, Nilsen R, Jonsson R, Bjune GIn situ expression of cytokines and cellular phenotypes in the lungs of mice with slowly progressive primary tuberculosis. Scan J Immunol. 2000;51:548–56.[PubMed][Google Scholar]
26. Harigai M, Hara M, Yoshimura T, Leonard EJ, Inoue K, Kashiwazaki SMonocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. Clin Immunol Immunopathol. 1993;69:83–91.[PubMed][Google Scholar]
27. Shi MM, Chong IW, Long NC, Love JA, Godleski JJ, Paulauskis JDFunctional characterization of recombinant rat macrophage inflammatory protein-1 alpha and mRNA expression in pulmonary inflammation. Inflammation. 1998;22:29–43.[PubMed][Google Scholar]
28. Kim JJ, Nottingham LK, Sin JI, et al CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines. J Clin Invest. 1998;102:1112–24.[Google Scholar]
29. Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SLRole of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol. 1996;157:4602–8.[PubMed][Google Scholar]
30. Lukacs NW, Chensue SW, Karpus WJ, Lincoln P, Keefer C, Strieter RM, Kunkel SLC-C chemokines differentially alter interleukin-4 production from lymphocytes. Am J Pathol. 1997;150:1861–8.[Google Scholar]
31. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJControl of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 2000;404:407–11.[PubMed][Google Scholar]
32. Tedla N, Wang HW, McNeil HP, Di Girolamo N, Hampartzoumian T, Wakefield D, Lloyd ARegulation of T lymphocyte trafficking into lymph nodes during an immune response by the chemokines macrophage inflammatory protein (MIP) -1 alpha and MIP-1 beta. J Immunol. 1998;161:5663–72.[PubMed][Google Scholar]
33. Trumpfheller C, Tenner-Racz K, Racz P, Fleischer B, Frosch SExpression of macrophage inflammatory protein (MIP) -1α, MIP-1β, and RANTES genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine response. Clin Exp Immunol. 1998;112:92–9.[Google Scholar]
34. Schall TJ, Bacon K, Camp RD, Kaspari JW, Goeddel DVHuman macrophage inflammatory protein alpha (MIP-1alpha) and MIP-1beta chemokines attract distinct populations of lymphocytes. J Exp Med. 1993;177:1821–6.[Google Scholar]
35. Diab A, Abdalla H, Li HL, et al Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1alpha attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis. Infect Immun. 1999;67:2590–601.[Google Scholar]
36. Lee SC, Brummet ME, Shahabuddin S, et al Cutaneous injection of human subjects with macrophage inflammatory protein-1 alpha induces significant recruitment of neutrophils and monocytes. J Immunol. 2000;164:3392–401.[PubMed][Google Scholar]
37. Johnston B, Burns AR, Suematsu M, Issekutz TB, Woodman RC, Kubes PChronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. J Clin Invest. 1999;103:1269–76.[Google Scholar]
38. Madianos PN, Papapanou PN, Sandros J. Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration. Infect Immun. 1997;65:3983–90.
39. Tonetti MS, Imboden MA, Gerber L, Lang NP, Laissue J, Mueller CLocalized expression of mRNA for phagocytic-specific chemotactic cytokines in human periodontal infections. Infect Immun. 1994;62:4005–14.[Google Scholar]
40. Farber JMMig and IP-10: CXC chemokines that target lymphocytes. J Leukoc Biol. 1997;61:246–57.[PubMed][Google Scholar]
41. Gangur V, Simons FE, Hayglass KTHuman IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses. FASEB J. 1998;12:705–13.[PubMed][Google Scholar]
42. Muhl H, Dinarello CAMacrophage inflammatory protein-1 alpha production in lipopolysaccharide-stimulated human adherent blood mononuclear cells is inhibited by the nitric oxide synthase inhibitor N (G)-monomethyl-l-arginine. J Immunol. 1997;159:5063–9.[PubMed][Google Scholar]
43. Birkedal-Hansen HRoles of cytokines and inflammatory mediators in tissue destruction. J Periodont Res. 1993;28:500–10.[PubMed][Google Scholar]