A Hyperactive Neutrophil Phenotype in Aggressive Periodontitis

  • Kim, Kap-Yul (Department of Immunology & Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kim, Min-Kyung (Department of Periodontology, BK21 CLS, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Choi, Yun-Sik (Department of Immunology & Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kim, Yong-Cheol (Department of Immunology & Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Jo, Ah-Ram (Department of Immunology & Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Rhyu, In-Chul (Department of Periodontology, BK21 CLS, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Choi, Young-Nim (Department of Immunology & Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University)
  • 투고 : 2012.05.16
  • 심사 : 2012.06.19
  • 발행 : 2012.06.30

초록

Although neutrophils function in both defense and tissue destruction, their defensive roles have rarely been studied in association with periodontitis. We hypothesized that peripheral neutrophils are pre-activated in vivo in periodontitis and that hyperactive neutrophils would show enhanced phagocytic ability as well as an increased production of reactive oxygen species (ROS). Peripheral blood neutrophils from patients with aggressive periodontitis and age/gender-matched healthy subjects (10 pairs) were isolated. The levels of CD11b and CD64 expression on the neutrophils and the level of plasma endotoxin were determined by flow cytometry and a limulus amebocyte lysate test, respectively. In addition, neutrophils were subjected to a flow cytometric phagocytosis assay and luminol-enhanced chemiluminescence for non-opsonized Fusobacterium nucleatum in parallel. The neutrophilsfrom most patients expressed increased levels of both CD11b and CD64. In addition, the plasma from these patients tended to contain a higher level of endotoxin than the healthy controls. In contrast, no differences were found between the two groups with regard to phagocytosis or ROS generation by F. nucleatum. The ability to phagocytose F. nucleatum was found to positively correlate with the ability to produce ROS. In conclusion, peripheral neutrophils from patients with aggressive periodontitis are hyperactive but not hyperreactive to F. nucleatum.

키워드

참고문헌

  1. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232.
  2. Asman B. Peripheral PMN cells in juvenile periodontitis. Increased release of elastase and of oxygen radicals after stimulation with opsonized bacteria. J Clin Periodontol. 1988;15:360-4.
  3. Gustafsson A, Asman B. Increased release of free oxygen radicals from peripheral neutrophils in adult periodontitis after Fc gamma-receptor stimulation. J Clin Periodontol. 1996;23:38-44.
  4. Matthews JB, Wright HJ, Roberts A, Cooper PR, Chapple IL. Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis. Clin Exp Immunol. 2007;147:255-64.
  5. Fredriksson MI, Gustafsson AK, Bergstrom KG, Asman BE. Constitutionally hyperreactive neutrophils in periodontitis. J Periodontol. 2003;74:219-24.
  6. Matthews JB, Wright HJ, Roberts A, Ling-Mountford N, Cooper PR, Chapple IL. Neutrophil hyper-responsiveness in periodontitis. J Dent Res. 2007;86:718-22.
  7. Leino L, Hurttia HM, Sorvajarvi K, Sewon LA. Increased respiratory burst activity is associated with normal expression of IgG-Fc-receptors and complement receptors in peripheral neutrophils from patients with juvenile periodontitis. J Periodontal Res. 1994;29:179-84.
  8. Kobayashi T, Westerdaal NA, Miyazaki A, van der Pol WL, Suzuki T, Yoshie H, van de Winkel JG, Hara K. Relevance of immunoglobulin G Fc receptor polymorphism to recurrence of adult periodontitis in Japanese patients. Infect Immun. 1997;65:3556-60.
  9. Kobayashi T, Sugita N, van der Pol WL, Nunokawa Y, Westerdaal NA, Yamamoto K, van de Winkel JG, Yoshie H. The Fcgamma receptor genotype as a risk factor for generalized early-onset periodontitis in Japanese patients. J Periodontol. 2000;71:1425-32.
  10. Nibali L, Parkar M, Brett P, Knight J, Tonetti MS, Griffiths GS. NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study. J Clin Periodontol. 2006;33:529-39.
  11. Nicu EA, Van der Velden U, Everts V, Van Winkelhoff AJ, Roos D, Loos BG. Hyper-reactive PMNs in FcgammaRIIa 131 H/H genotype periodontitis patients. J Clin Periodontol. 2007;34:938-45
  12. Gustafsson A, Asman B, Bergstrom K. Priming response to inflammatory mediators in hyperreactive peripheral neutrophils from adult periodontitis. Oral Dis. 1997;3:167-71.
  13. Borregaard N, Kjeldsen L, Sengelov H, Diamond MS, Springer TA, Anderson HC, Kishimoto TK, Bainton DF. Changes in subcellular localization and surface expression of L-selectin, alkaline phosphatase, and Mac-1 in human neutrophils during stimulation with inflammatory mediators. J Leukoc Biol. 1994;56:80-7.
  14. Borregaard N. Neutrophils, from marrow to microbes. Immunity. 2010;33:657-70.
  15. Sengelov H, Kjeldsen L, Diamond MS, Springer TA, Borregaard N. Subcellular localization and dynamics of Mac-1 (alpha m beta 2) in human neutrophils. J Clin Invest. 1993;92:1467-76.
  16. Nuutila J. The novel applications of the quantitative analysis of neutrophil cell surface FcgammaRI (CD64) to the diagnosis of infectious and inflammatory diseases. Curr Opin Infect Dis. 2010;23:268-74
  17. Jalava-Karvinen P, Hohenthal U, Laitinen I, Kotilainen P, Rajamäki A, Nikoskelainen J, Lilius EM, Nuutila J. Simultaneous quantitative analysis of Fc gamma RI (CD64) and CR1 (CD35) on neutrophils in distinguishing between bacterial infections, viral infections, and inflammatory diseases. Clin Immunol. 2009;133:314-23.
  18. Nishihara T, Koseki T. Micobial etiology of periodontitis. Periodontol 2000. 2004;36:14-6.
  19. Shin JE, Ji S, Choi Y. Ability of oral bacteria to induce tissue-destructive molecules from human neutrophils. Oral Dis. 2008; 14: 327-34.
  20. van der Meer W, Pickkers P, Scott CS, van der Hoeven JG, Gunnewiek JK. Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia. J Endotoxin Res. 2007;13:94-100.
  21. Kim YC, Shin JE, Lee SH, Chung WJ, Lee YS, Choi BK, Choi Y. Memrane-bound proteinase 3 and PAR2 mediate phagocytosis of non-opsonized bacteria in human neutrophils. Mol Immunol. 2011;48:1966-74.
  22. Johnstone AM, Koh A, Goldberg MB, Glogauer M. A hyperactive neutrophil phenotype in patients with refractory periodontitis. J Periodontol. 2007;78:1788-94.
  23. Geerts SO, Nys M, De MP, Charpentier J, Albert A, Legrand V, Rompen EH. Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. J Periodontol. 2002;73:73-8.
  24. Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, Willeit J. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol. 1999;34:1975-81.
  25. Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Backhed F. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A. 2011;108 Suppl1:4592-8.
  26. Brechard S, Tschirhart EJ. Regulation of superoxide production in neutrophils: role of calcium influx. J Leukoc Biol. 2008;84:1223-37.
  27. Ivan E, Colovai AI. Human Fc receptors: critical targets in the treatment of autoimmune diseases and transplant rejections. Hum Immunol. 2006;67:479-91.
  28. Fredriksson M, Gustafsson A, Asman B, Bergstrom K. Hyper-reactive peripheral neutrophils in adult periodontitis: generation of chemiluminescence and intracellular hydrogen peroxide after in vitro priming and FcgammaR-stimulation. J Clin Periodontol. 1998;25:394-8.
  29. Pricop L, Salmon JE. Redox regulation of Fcgamma receptor-mediated phagocytosis: implications for host defense and tissue injury. Antioxid Redox Signal. 2002;4:85-95.