Skip to main content

Advertisement

Log in

Human β-Defensins in different states of diseases of the tonsilla palatina

  • Miscellaneous
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Tonsils are believed to play an important role during the development of the immune system. Although diseases of the tonsils like hypertrophy of the tonsil, acute tonsillitis, chronic tonsillitis or peritonsillar abscess are common, little is known about the underlying pathophysiology. Little is known about antimicrobial peptides produced by the tonsils. The human β-Defensins 1-3 (hBD1-3) are naturally produced “antibiotics” with antimicrobial activity against different bacteria, fungi, and viruses. The objective of the study was to determine the concentrations for hBD1-3 in different states of diseases of the tonsilla palatina. After tonsillectomy and tissue fixation in formalin, total proteins were isolated from 38 samples (11 hypertrophy of the tonsil, 8 acute tonsillitis, 11 chronic tonsillitis, 8 peritonsillar abscesses). The protein concentration was determined and ELISA for hBD1-3 were performed. We also conducted immunofluorescence double stainings for the co-expression of streptococcus group A and hBD1-3. We could verify a significant difference for the mean hBD1 score of the acute tonsillitis in comparison to the hyperplastic tonsil, the chronic tonsillitis, and the peritonsillar abscess. There was no statistically significant difference in the hBD2 and hBD3 concentrations between the four groups. The immunofluorescence stainings showed that hBD1-3 and the streptococcus group A in the same place. We conclude that in the hyperplastic tonsilla palatina hBD1-3 play an important role. The mouth is constantly faced with a high bacterial load. During a tonsillitis, the hBD1 concentration is lower than in the non-acute infected tonsil because hBD1 is being consumed for fighting the bacterial infection. But, the existence of hBD1-3 in the tonsil cannot prevent the tonsillitis to become chronic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  1. Junqueira LC, Carneiro J (eds) (1991) Tonsils (Basic Histology), 3rd edn. Springer, Berlin

    Google Scholar 

  2. Houck JR, Rhodes RE (2003) Immunology and allergy. In: Lee KJ (ed) Essential otolaryngology head and neck surgery. McGraw-Hill, New York, pp 258–263

    Google Scholar 

  3. Rohling I (2002) Gesundheit und Entwicklungsstand der Osnabrücker Schulanfänger-Multifaktorielle Analyse der Ergebnisse der Schuleingangsuntersuchungen unter besonderer Berücksichtigung des Jahrgangs 2001; Stadt Osnabrück Fachbereich Soziales und Gesundheit Gesundheitsamt/Jugendärztlicher Dienst; Februar

  4. Van Den Akker EH, Hoes AW, Burton MJ, Schilder AG (2004) Large international differences in (adeno) tonsillectomy rates. Clin Otolaryngol Allied Sci 29(2):161–164

    Article  Google Scholar 

  5. Bundesauswertung (2003) Modul 07/1: Tonsillektomie Qualitätsindikatoren; © BQS Bundesgeschäftsstelle Qualitätssicherung gGmbH 2004; http://www.bqs-online.com/outcome/2003/ergebnisse/leistungsbereiche/tonsillektomie/bundesauswertung/bu_Tonsillek.pdf

  6. Vestergaard H, Wohlfahrt J, Westergaard T, Pipper C, Rasmussen N, Melbye M (2007) Incidence of tonsillectomy in Denmark, 1980 to 2001. Pediatr Infect Dis J 26(12):1117–1121

    Article  PubMed  Google Scholar 

  7. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395

    Article  CAS  PubMed  Google Scholar 

  8. Bensch K, Raida M, Magert H-J, Schulz-Knappe P, Forssmann W-G (1995) hBD-1: a novel β-defensin from human plasma. FEBS Lett 368:331–335

    Article  CAS  PubMed  Google Scholar 

  9. McCray P Jr, Bentley L (1997) Human airway epithelia express a β-defensin. Am J Respir Cell Mol Biol 16:343–349

    CAS  PubMed  Google Scholar 

  10. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM (1997) Human β-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553–560

    Article  CAS  PubMed  Google Scholar 

  11. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human β-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642

    Article  CAS  PubMed  Google Scholar 

  12. Zhao CQ, Wang I, Lehrer RI (1996) Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396:319–332

    Article  CAS  PubMed  Google Scholar 

  13. Sørensen OE, Cowland JB, Theilgaard-Mönch K, Liu L, Ganz T, Borregaard N (2003) Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol 170:5583–5589

    PubMed  Google Scholar 

  14. Hiratsuka T, Mukae H, Iiboshi H, Ashitani J, Nabeshima K, Minematsu T, Chino N, Ihi T, Kohno S, Nakazato M (2003) Increased concentrations of human-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 58:425

    Article  CAS  PubMed  Google Scholar 

  15. Zhu BD, Feng Y, Huang N, Wu Q, Wang BY (2003) Mycobacterium bovis bacille Calmette-Guerin (BCG) enhances human-defensin-1 gene transcription in human pulmonary gland epithelial cells. Acta Pharmacol Sin 24:907

    CAS  PubMed  Google Scholar 

  16. Sørensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T (2005) Differential regulation of defensin expression in human skin by microbial stimuli. J Immunol 174:4870–4879

    PubMed  Google Scholar 

  17. Krisanaprakornkit S, Weinberg A, Perez CN et al (1998) Expression of the peptide antibiotic human β-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun 66:4222–4228

    CAS  PubMed  Google Scholar 

  18. Schröder J-M, Harder J (1999) Human beta-defensin-2. Int J Biochem Cell Biol 31(6):645–651

    Article  PubMed  Google Scholar 

  19. Sørensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T (2005) Differential regulation of defensin expression in human skin by microbial stimuli. J Immunol 174:4870–4879

    PubMed  Google Scholar 

  20. Uehara N, Yagihashi A, Kondoh K, Tsuji N, Fujita T, Hamada H, Watanabe N (2003) Human beta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression. J Med Microbiol 52:41–45

    Article  CAS  PubMed  Google Scholar 

  21. Goldman M, Anderson G, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM (1997) Human beta-defensin-1 is a salt sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553–560

    Article  CAS  PubMed  Google Scholar 

  22. Harder J, Bartels J, Christophers E, Schröder JM (2001) Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem Vol 276(8):5707–5713

    Article  CAS  Google Scholar 

  23. Ishimoto H, Mukae H, Date Y, Shimbara T, Mondal MS, Ashitani J, Hiratsuka T, Kubo S, Kohno S, Nakazato M (2006) Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia. Eur Respir J 27(2):253–260

    Article  CAS  PubMed  Google Scholar 

  24. Schwaab M, Euteneuer S, Lautermann J, Sudhoff H (2005) Muramidase and lactoferrin in adenoidal hypertrophies, hypertrophic and chronic infected tonsil tissue—a quantitative analysis. Laryngorhinootologie 84(9):660–664

    Article  CAS  PubMed  Google Scholar 

  25. Ball SL, Siou GP, Wilson JA, Howard A, Hirst BH, Hall J (2007) Expression and immunolocalisation of antimicrobial peptides within human palatine tonsils. J Laryngol Otol 121(10):973–978

    Article  CAS  PubMed  Google Scholar 

  26. Meyer JE, Beier UH, Goeroegh T, Schreiber S, Beck C, Maune S (2006) Defensin and chemokine expression patterns in the palatine tonsil: a model of their local interaction. Eur Arch Otorhinolaryngol 263:319–326

    Article  PubMed  Google Scholar 

  27. Weise JB, Meyer JE, Helmer H, Wittrock H, Maune S (2002) A newly discovered function of palatine tonsils in immune defence: the expression of defensins. Otolaryngol Pol 56(4):409–413

    CAS  PubMed  Google Scholar 

  28. Schwaab M, Hansen S, Pearson MD, Shagdarsuren S, Dazert S (2009) Human beta-defensins-at the front line of the peritonsillar abscess. Eur J Clin Microbiol Infect Dis 28(7):745–755

    Article  CAS  PubMed  Google Scholar 

  29. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150(1):76–85

    Article  CAS  PubMed  Google Scholar 

  30. Wiechelmann KJ, Braun RD, Fitzpatrick JD (1988) Investigation of the bicinchoninic acid protein assay: identification of the groups responsible for color formation. Anal Biochem 175(1):231–237

    Article  Google Scholar 

  31. Cohen J (2002) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Assoc Inc., Hillsdale, NJ Auflage: 2002

    Google Scholar 

  32. Becker KF, Schott C, Hipp S, Metzger V, Porschewski P, Beck R, Nährig J, Becker I, Höfler H (2007) Quantitative protein analysis from formalin-fixed tissues: implications for translational clinical research and nanoscale molecular diagnosis. J Pathol 3:370–378

    Article  Google Scholar 

  33. Kroll J, Becker KF, Kuphal S, Hein R, Hofstädter F, Bosserhoff AK (2008) Isolation of high quality protein samples from punches of formalin fixed and paraffin embedded tissue blocks. Histol Histopathol 4:391–395

    Google Scholar 

  34. Casselbrant ML (1999) What is wrong in chronic adenoiditis/tonsillitis anatomical considerations. Int J Pediatr Otorhinolaryngol 49(Suppl 1):S133–S135

    Article  PubMed  Google Scholar 

  35. Durr M, Peschel A (2002) Chemokines meet defensins: the merging concepts of chemoattractants and antimicrobial peptides in host defense. Infect Immun 70:6515–6517

    Article  CAS  PubMed  Google Scholar 

  36. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528

    Article  CAS  PubMed  Google Scholar 

  37. Schröder J-M (1999) Clinical significance of epithelial peptide antibiotics. Bio Drugs 11(5):293–300

    Google Scholar 

  38. Brook I (2005) The role of anaerobic bacteria in tonsillitis. Int J Pediatr Otorhinolaryngol 69(1):9–19

    Article  PubMed  Google Scholar 

  39. Brook I (2001) The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis. Int J Antimicrob Agents 17:439–442

    Article  CAS  PubMed  Google Scholar 

  40. Ouhara K, Komatsuzawa H, Yamada S, Shiba H, Fujiwara T, Ohara M, Sayama K, Hashimoto K, Kurihara H, Sugai M (2005) Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cells. J Antimicrob Chemother 55:888–896

    Article  CAS  PubMed  Google Scholar 

  41. Chen X, Niyonsaba F, Ushio H, Okuda D, Nagaoka I, Ikeda S, Okumura K, Ogawa H (2005) Synergistic effect of antibacterial agents human beta-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli. J Dermatol Sci 40(2):123–132

    Article  CAS  PubMed  Google Scholar 

  42. Maisetta G, Batoni G, Esin S, Luperini F, Pardini M, Bottai D, Florio W, Giuca MR, Gabriele M, Campa M (2003) Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother 47(10):3349–3351

    Article  CAS  PubMed  Google Scholar 

  43. Claeys S, de Belder T, Holtappels G, Gevaert P, Verhasselt B, van Cauwenbergr P et al (2003) Human beta-defensins and toll-like receptors in the upper airway. Allergy 58:748–753

    Article  CAS  PubMed  Google Scholar 

  44. Chole RA, Faddis BT (2003) Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity. Arch Otolaryngol Head Neck Surg 129(6):634–636

    Article  PubMed  Google Scholar 

  45. Kania RE, Lamers GE, Vonk MJ, Huy PT, Hiemstra PS, Bloemberg GV, Grote JJ (2007) Demonstration of bacterial cells and glycocalyx in biofilms on human tonsils. Arch Otolaryngol Head Neck Surg 133(2):115–121

    Article  PubMed  Google Scholar 

  46. Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284(5418):1318–1322

    Article  CAS  PubMed  Google Scholar 

  47. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358(9276):135–138

    Article  CAS  PubMed  Google Scholar 

  48. Gorfien JL, Noble B, Brodsky L (2001) Comparison of the microanatomical distributions of macrophages and dendritic cells in normal and diseased tonsils. Ann Otol Rhinol Laryngol 110(2):173–182

    CAS  PubMed  Google Scholar 

  49. Le TM, Rovers MM, van Staaij BK, van den Akker EH, Hoes AW, Schilder AG (2007) Alterations of the oropharyngeal microbial flora after adenotonsillectomy in children: a randomized controlled trial. Arch Otolaryngol Head Neck Surg 133(10):969–972

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We would like to thank Mrs. S. Kanabey for helping with the protein isolation and the institute of pathology of the Ruhr-University of Bochum for providing us with the in formalin fixated tissues. We hereby declare that the experiments comply with the current laws of the country in which they were performed. Parts of this study will be reported at the 80th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery, May 20–24th, 2009 Hanse Messe Rostock, Germany. This study was supported by the Ruhr-University Bochum (FORUM).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthias Schwaab.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwaab, M., Gurr, A., Hansen, S. et al. Human β-Defensins in different states of diseases of the tonsilla palatina. Eur Arch Otorhinolaryngol 267, 821–830 (2010). https://doi.org/10.1007/s00405-009-1086-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-009-1086-5

Keywords

Navigation