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Abstract

The external auditory canal is vulnerable to bacterial infections, but little is known about thechemical compositions of ear wax regarding antimicrobial peptides. We, therefore, studied the proteinconcentrations of ten well-known human antimicrobial peptides from ear wax.Twenty ear wax samples from healthy individuals were analysed using enzyme-linked immunosorbent assay (ELISA) to determine theprotein concentrations of the antimicrobial peptides hBD1-3, lactoferrin, LL-37, BPI, hSLPI and HNP1-3. All ten antimicrobial peptides are present in ear wax. Some of these proteins seem to be merelycell-bound in ear wax. Antimicrobial peptides in ear wax prevent bacteria and fungi from causing infections inthe external auditory canal. The role and importance of these proteins for the blind-ending ear externalcanal is discussed. If this local defence system fails, infections of the external auditory canal may result.The knowledge about the presence of antimicrobial peptides in cerumen may lead to new concepts ofthe local treatment of external auditory canal diseases in the future.

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References

  1. Cole AM, Dewan P, Ganz T (1999) Innate antimicrobial activity of nasal secretions. Infect Immun 67:3267–3275

    PubMed  CAS  Google Scholar 

  2. Hiemstra PS (2007) The role of epithelial beta-defensins and cathelicidins in host defense of the lung. Exp Lung Res 33(10):537–542

    Article  PubMed  CAS  Google Scholar 

  3. Beisswenger C, Bals R (2005) Antimicrobial peptides in lung inflammation. Chem Immunol Allerg 86:55–71

    Article  CAS  Google Scholar 

  4. Shai Y, Makovitzky A, Avrahami D (2006) Host defense peptides and lipopeptides: modes of action and potential candidates for the treatment of bacterial and fungal infections. Curr Protein Pept Sci 7(6):479–486

    Article  PubMed  CAS  Google Scholar 

  5. Koczulla AR, Bals R (2003) Antimicrobial peptides: current status and therapeutic potential. Drugs 63:389–406

    Article  PubMed  CAS  Google Scholar 

  6. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 22:181–215

    Article  PubMed  Google Scholar 

  7. Yang D, Biragyn A, Kwak LW, Oppenheim JJ (2002) Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 23:291–296

    Article  PubMed  CAS  Google Scholar 

  8. Bensch KW, Raida M, Mägert HJ, Schulz-Knappe P, Forssmann WG (1995) hBD-1: a novel beta-defensin from human plasma. FEBS Lett 368:331–335

    Article  PubMed  CAS  Google Scholar 

  9. 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 

  10. Goldman MJ, Anderson GM, 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  PubMed  CAS  Google Scholar 

  11. Krisanaprakornkit S, Weinberg A, Perez CN, Dale BA (1998) Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun 66(9):4222–4228

    PubMed  CAS  Google Scholar 

  12. Schneider JJ, Unholzer A, Schaller M, Schäfer-Korting M, Korting HC (2005) Human defensins. J Mol Med 83(8):587–595, Epub 2005 Apr 9

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  15. 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. 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 beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 58:425–430

    Article  PubMed  CAS  Google Scholar 

  18. Bals R, Wang X, Zasloff M, Wilson JM (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 95:9541–9546

    Article  PubMed  CAS  Google Scholar 

  19. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jörnvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96(9):3086–3093, Nov 1

    PubMed  CAS  Google Scholar 

  20. Wang Y, Walter G, Herting E, Agerberth B, Johansson J (2004) Antibacterial activities of the cathelicidins prophenin (residues 62 to 79) and LL-37 in the presence of a lung surfactant preparation. Antimicrob Agents Chemother 48(6):2097–2100, Jun

    Article  PubMed  CAS  Google Scholar 

  21. Frohm Nilsson M, Sandstedt B, Sørensen O, Weber G, Borregaard N, Ståhle-Bäckdahl M (1999) The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 67(5):2561–2566

    PubMed  CAS  Google Scholar 

  22. Agerberth B, Gunne H, Odeberg J, Kogner P, Boman HG, Gudmundsson GH (1995) FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc Natl Acad Sci USA 92:195–199

    Article  PubMed  CAS  Google Scholar 

  23. Travis SM, Anderson NN, Forsyth WR, Espiritu C, Conway BD, Greenberg EP, McCray PB Jr, Lehrer RI, Welsh MJ, Tack BF (2000) Bactericidal activity of mammalian cathelicidin-derived peptides. Infect Immun 68:2748–2755

    Article  PubMed  CAS  Google Scholar 

  24. Koczulla R, von Degenfeld G, Kupatt C, Krötz F, Zahler S, Gloe T, Issbrücker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111(11):1665–1672

    Article  PubMed  CAS  Google Scholar 

  25. von Haussen J, Koczulla R, Shaykhiev R, Herr C, Pinkenburg O, Reimer D, Wiewrodt R, Biesterfeld S, Aigner A, Czubayko F, Bals R (2008) The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells. Lung Cancer 59(1):12–23, Epub 2007 Aug 31

    Article  Google Scholar 

  26. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63:1291–1297

    PubMed  CAS  Google Scholar 

  27. Abe T, Kobayashi N, Yoshimura K, Trapnell BC, Kim H, Hubbard RC, Brewer MT, Thompson RC, Crystal RG (1991) Expression of the secretory leukoprotease inhibitor gene in epithelial cells. J Clin Invest 87(6):2207–2215

    Article  PubMed  CAS  Google Scholar 

  28. Brown A, Farmer K, MacDonald L, Kalsheker N, Pritchard D, Haslett C, Lamb J, Sallenave JM (2003) House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors. Am J Respir Cell Mol Biol 29(3 Pt 1):381–389

    Article  PubMed  CAS  Google Scholar 

  29. Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH (1996) Antibacterial activity of antileukoprotease. Infect Immun 64(11):4520–4524

    PubMed  CAS  Google Scholar 

  30. Wahl SM, McNeely TB, Janoff EN, Shugars D, Worley P, Tucker C, Orenstein JM (1997) Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I. Oral Dis 3(Suppl 1):S64–S69

    PubMed  Google Scholar 

  31. Weiss J, Elsbach P, Olsson I, Odeberg H (1978) Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 253:2664–2672

    PubMed  CAS  Google Scholar 

  32. Ooi CE, Weiss J, Elsbach P, Frangione B, Mannion B (1987) A 25-kDa NH2-terminal fragment carries all the antibacterial activities of the human neutrophil 60-kDa bactericidal/permeability-increasing protein. J Biol Chem 262:14891–14894

    PubMed  CAS  Google Scholar 

  33. Reichel PH, Seemann C, Csernok E, Schröder JM, Müller A, Gross WL, Schultz H (2003) Bactericidal/permeability-increasing protein is expressed by human dermal fibroblasts and upregulated by interleukin 4. Clin Diagn Lab Immunol 10:473–475

    PubMed  CAS  Google Scholar 

  34. Peuravuori H, Aho VV, Aho HJ, Collan Y, Saari KM (2006) Bactericidal/permeability-increasing protein in lacrimal gland and in tears of healthy subjects. Graefes Arch Clin Exp Ophthalmol 244:143–148

    Article  PubMed  CAS  Google Scholar 

  35. von der Möhlen MA, Kimmings AN, Wedel NI, Mevissen ML, Jansen J, Friedmann N, Lorenz TJ, Nelson BJ, White ML, Bauer R, Hack CE, Eerenberg AJM, van Deventer SJH (1995) Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. J Infect Dis 172:144–151

    Article  PubMed  Google Scholar 

  36. Demetriades D, Smith JS, Jacobson LE, Moncure M, Minei J, Nelson BJ, Scannon PJ (1999) Bactericidal/permeability-increasing protein (rBPI21) in patients with hemorrhage due to trauma: results of a multicenter phase II clinical trial. rBPI21 Acute Hemorrhagic Trauma Study Group. J Trauma 46:667–676

    Article  PubMed  CAS  Google Scholar 

  37. Levin M, Quint PA, Goldstein B, Barton P, Bradley JS, Shemie SD, Yeh T, Kim SS, Cafaro DP, Scannon PJ, Giroir BP (2000) Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 356:961–7

    Article  PubMed  CAS  Google Scholar 

  38. Giroir BP, Quint PA, Barton P, Kirsch EA, Kitchen L, Goldstein B, Nelson BJ, Wedel NJ, Carroll SF, Scannon PJ (1997) Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet 350:1439–1443

    Article  PubMed  CAS  Google Scholar 

  39. Stenfors LE, Bye HM, Räisänen S (2002) Immunocytochemical localization of lysozyme and lactoferrin attached to surface bacteria of the palatine tonsils during infectious mononucleosis. J Laryngol Otol 116(4):264–268

    Article  PubMed  Google Scholar 

  40. Yamauchi K, Tomita M, Giehl TJ, Ellison RT 3rd (1993) Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect Immun 61(2):719–728

    PubMed  CAS  Google Scholar 

  41. Otto BR, Verweij-van Vught AM, MacLaren DM (1992) Transferrins and heme-compounds as iron sources for pathogenic bacteria. Crit Rev Microbiol 18(3):217–233

    Article  PubMed  CAS  Google Scholar 

  42. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427–1435

    Article  PubMed  CAS  Google Scholar 

  43. Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, Eriksson EE, Herwald H, Agerberth B, Lindbom L (2008) Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 118:3491–3502

    Article  PubMed  CAS  Google Scholar 

  44. Aarbiou J, Ertmann M, van Wetering S, van Noort P, Rook D, Rabe KF, Litvinov SV, van Krieken JH, de Boer WI, Hiemstra PS (2002) Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J Leukoc Biol 72:167–174

    PubMed  CAS  Google Scholar 

  45. Murphy CJ, Foster BA, Mannis MJ, Selsted ME, Reid TW (1993) Defensins are mitogenic for epithelial cells and fibroblasts. J Cell Physiol 155:408–413

    Article  PubMed  CAS  Google Scholar 

  46. Alvord LS, Farmer BL (1997) Anatomy and orientation of the human external ear. J Am Acad Audiol 8(6):383–390

    PubMed  CAS  Google Scholar 

  47. Overfield T (1985) Biologic variation in health and illness: race, age, and sex differences. Addison-Wesley Publishing, Menlo Park, CA

    Google Scholar 

  48. Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N (2006) A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet 38(3):324–330, Epub 2006 Jan 29

    Article  PubMed  CAS  Google Scholar 

  49. Bass EJ, Jackson JF (1977) Cerumen types in Eskimos. Am J Phys Anthropol 47(2):209–210

    Article  PubMed  CAS  Google Scholar 

  50. Ibraimov AI (1991) Cerumen phenotypes in certain populations of Eurasia and Africa. Am J Phys Anthropol 84(2):209–211, Feb

    PubMed  CAS  Google Scholar 

  51. Mendelian Inheritance in Man. Available online at: http://en.wikipedia.org/wiki/Mendelian_Inheritance_in_Man. Accessed 1 December 2010

  52. Burkhart CN, Kruge MA, Burkhart CG, Black C (2001) Cerumen composition by flash pyrolysis-gas chromatography/mass spectrometry. Otol Neurotol 22(6):715–722

    Article  PubMed  CAS  Google Scholar 

  53. Bortz JT, Wertz PW, Downing DT (1990) Composition of cerumen lipids. J Am Acad Dermatol 23(5):845–849

    Article  PubMed  CAS  Google Scholar 

  54. Okuda I, Bingham B, Stoney P, Hawke M (1991) The organic composition of earwax. J Otolaryngol 20(3):212–215, Jun

    PubMed  CAS  Google Scholar 

  55. Roeser RJ, Ballachanda BB (1997) Physiology, pathophysiology, and anthropology/epidemiology of human earcanal secretions. J Am Acad Audiol 8:391–400

    PubMed  CAS  Google Scholar 

  56. Creed E, Negus VE (1926) Investigations regarding the function of aural cerumen. J Laryngol Otol 41:223–230

    Article  Google Scholar 

  57. Nichols AC, Perry ET (1956) Studies on the growth of bacteria in the human ear canal. J Invest Dermatol 27:165–170

    PubMed  CAS  Google Scholar 

  58. Singer DE, Freeman E, Hoffert WR, Keys RJ, Mitchell RB, Hardy AV (1956) Otitis externa: bacteriological and mycological studies. Ann Otol Rhinol Laryngol 61:317–330

    Google Scholar 

  59. Campos A, Betancor L, Arias A, Rodríguez C, Hernández AM, López Aguado D, Sierra A (2000) Influence of human wet cerumen on the growth of common and pathogenic bacteria of the ear. J Laryngol Otol 114(12):925–929, Dec

    Article  PubMed  CAS  Google Scholar 

  60. Hyslop NE Jr (1971) Ear wax and host defense. N Engl J Med 284:1099–1100

    Article  PubMed  Google Scholar 

  61. Petrakis NL, Doherty M, Lee RE, Smith SC, Page NL (1971) Demonstration and implications of lysozyme and immunoglobulins in human ear wax. Nature 229:119–120

    Article  PubMed  CAS  Google Scholar 

  62. Chai TJ, Chai TC (1980) Bactericidal activity of cerumen. Antimicrob Agents Chemother 18(4):638–641

    PubMed  CAS  Google Scholar 

  63. Lum CL, Jeyanthi S, Prepageran N, Vadivelu J, Raman R (2009) Antibacterial and antifungal properties of human cerumen. J Laryngol Otol 123:375–378, Aug

    Article  PubMed  CAS  Google Scholar 

  64. Pata YS, Ozturk C, Akbas Y, Gorur K, Unal M, Ozcan C (2003) Has cerumen a protective role in recurrent external otitis? Am J Otolaryngol 24(4):209–212, Jul–Aug

    Article  PubMed  Google Scholar 

  65. Stone M, Fulghum RS (1984) Bactericidal activity of wet cerumen. Ann Otol Rhinol Laryngol 93(2 Pt 1):183–186, Mar–Apr

    PubMed  CAS  Google Scholar 

  66. Stoeckelhuber M, Matthias C, Andratschke M, Stoeckelhuber BM, Koehler C, Herzmann S, Sulz A, Welsch U (2006) Human ceruminous gland: ultrastructure and histochemical analysis of antimicrobial and cytoskeletal components. Anat Rec A Discov Mol Cell Evol Biol 288:877–884

    PubMed  Google Scholar 

  67. Meyer JE, Schwaab M, Beier UH, Görögh T, Buchelt T, Frese K, Maune S (2006) Association between human beta defensin expression and cholesteatoma formation. Auris Nasus Larynx 33(2):159–165, Epub 2006 Jan 23

    Article  PubMed  Google Scholar 

  68. Bøe R, Silvola J, Yang J, Moens U, McCray PB Jr, Stenfors LE, Seljfelid R (1999) Human beta-defensin-1 mRNA is transcribed in tympanic membrane and adjacent auditory canal epithelium. Infect Immun 67(9):4843–4846

    PubMed  Google Scholar 

  69. Yoon YJ, Jin Woo Park JW, Lee EJ (2008) Presence of hBD-1 and hBD-2 in human cerumen and external auditory canal skin. Acta Otolaryngol 128(8):871–875, Aug

    Article  PubMed  CAS  Google Scholar 

  70. Schwaab M, Hansen S, Gurr A, Schwaab T, Minovi A, Sudhoff H, Dazert S (2009) Protein isolation from ear wax made easy. Eur Arch Otorhinolaryngol 266(11):1699–1702, Epub 2009 Apr 4

    Article  PubMed  Google Scholar 

  71. Jung HH, Chae SW, Jung SK, Kim ST, Lee HM, Hwang SJ (2003) Expression of a cathelicidin antimicrobial peptide is augmented in cholesteatoma. Laryngoscope 113:432–435

    Article  PubMed  CAS  Google Scholar 

  72. Lee JK, Chae SW, Cho JG, Lee HM, Hwang SJ, Jung HH (2006) Expression of secretory leukocyte protease inhibitor in middle ear cholesteatoma. Eur Arch Otorhinolaryngol 263:1077–1081

    Article  PubMed  Google Scholar 

  73. Robinson AC, Hawke M, Naiberg J (1990) Impacted cerumen: a disorder of keratinocyte separation in the superficial external ear canal? J Otolaryngol 19(2):86–90

    PubMed  CAS  Google Scholar 

  74. Singh PK, Tack BF, McCray PB Jr, Welsh MJ (2000) Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 279(5):L799–L805

    PubMed  CAS  Google Scholar 

  75. 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, Epub 2005 Jun 15

    Article  PubMed  CAS  Google Scholar 

  76. Kim JK, Cho JH (2009) Change of external auditory canal pH in acute otitis externa. Ann Otol Rhinol Laryngol 118(11):769–772

    PubMed  Google Scholar 

  77. Weber PC, Roland PS, Hannley M, Friedman R, Manolidis S, Matz G, Owens F, Rybak L, Stewart MG (2004) The development of antibiotic resistant organisms with the use of ototopical medications. Otolaryngol Head Neck Surg 130(3 Suppl):S89–S94

    Article  PubMed  Google Scholar 

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Acknowledgement

Part of the data was reported at the annual meeting of the Association of Ear, Nose, and Throat Physicians of West Germany in Bochum, Germany, March 2010.

We thank Dr. med. M. D. Pearson for proofreading this manuscript and making corrections in his native language.

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The authors have declared that no conflict of interest exists. There was no sponsorship or funding arrangements relating to the research.

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Schwaab, M., Gurr, A., Neumann, A. et al. Human antimicrobial proteins in ear wax. Eur J Clin Microbiol Infect Dis 30, 997–1004 (2011). https://doi.org/10.1007/s10096-011-1185-2

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