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Table of Contents
Vol. 38, No. 3, 2004
Issue release date: May–June 2004
Section title: Paper
Caries Res 2004;38:247–253
(DOI:10.1159/000077762)

Salivary Proteins: Protective and Diagnostic Value in Cariology?

van Nieuw Amerongen A. · Bolscher J.G.M. · Veerman E.C.I.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands
email Corresponding Author

Abstract

Saliva is essential for a lifelong conservation of the dentition. Various functions of saliva are implicated in the maintenance of oral health and the protection of our teeth: (i) The tooth surface is continuously protected against wear by a film of salivary mucins and proline-rich glycoprotein. (ii) The early pellicle proteins, proline-rich proteins and statherin, promote remineralization of the enamel by attracting calcium ions. (iii) Demineralization is retarded by the pellicle proteins, in concert with calcium and phosphate ions in saliva and in the plaque fluid. (iv) Several salivary (glyco)proteins prevent the adherence of oral microorganisms to the enamel pellicle and inhibit their growth. (v) The salivary bicarbonate/carbonate buffer system is responsible for rapid neutralization of acids. An overview is presented on the major antimicrobial systems in human saliva. Not only the well-known major salivary glycoproteins, including mucins, proline-rich glycoprotein and immunoglobulins, but also a number of minor salivary (glyco)proteins, including agglutinin, lactoferrin, cystatins and lysozyme, are involved in the first line of defense in the oral cavity. Besides, small cationic antimicrobial peptides, e.g. defensins, cathelicidin and the histatins, have come into focus. These are potentially suited as templates for the design of a new generation of antibiotics, since they kill a broad spectrum of microorganisms, while hardly evoking resistance, in contrast to the classical antibiotics.

© 2004 S. Karger AG, Basel


  

Key Words

  • Agglutinin
  • Antimicrobial peptides
  • Cathelicidin
  • Histatins
  • Lactoferrin
  • Mucins
  • Saliva
  • Salivary proteins

References

  1. Abiko Y, Jinbu Y, Noguchi T, Nishimura M, Kusano K, Amaratunga P, Shibata T, Kaku T: Upregulation of human β-defensin 2 peptide expression in oral lichen planus, leukoplakia and candidiasis: An immunohistochemical study. Pathol Res Pract 2002;198:537–542.
  2. Bergey EJ, Cho MI, Hammarskjold ML, Rekosh D, Levine MJ, Blumberg BM, Epstein LG: Aggregation of human-immunodeficiency-virus type-1 by human salivary secretions. Crit Rev Oral Biol Med 1993a;4:467–474.
  3. Bergey EJ, Gu M, Collins AR, Bradway SD, Levine MJ: Modulation of herpes-simplex virus type-1 replication by human salivary secretions. Oral Microbiol Immunol 1993b;8:89–93.
  4. Bikker FJ, Ligtenberg AJM, Nazmi K, Veerman ECI, van ’t Hof W, Bolscher JGM, Poustka A, Nieuw Amerongen AV, Mollenhauer J: Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily. J Biol Chem 2002a;277:32109–32115.
  5. Bikker FJ, Ligtenberg AJM, van der Wal JE, van den Keijbus PAM, Holskov U, Veerman ECI, Nieuw Amerongen AV: Immunohistochemical detection of salivary agglutinin/gp-340 in human parotid, submandibular, and labial salivary glands. J Dent Res 2002b;81;134–139.
  6. Bobek LA, Tsai H, Biesbrock AR, Levine MJ: Molecular-cloning, sequence, and specificity of expression of the gene encoding the low-molecular-weight human salivary mucin (MUC7). J Biol Chem 1993;268:20563–20569.
  7. Bolscher JGM, Groenink J, van der Kwaak JS, van den Keijbus PAM, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Detection and quantification of MUC7 in submandibular, sublingual, palatine, and labial saliva by anti-peptide antiserum. J Dent Res 1999;78:1362–1369.
  8. Bolscher JGM, Nazmi K, Ran LJ, Van Engelenburg FAC, Schuitemaker H, Veerman ECI, Nieuw Amerongen AV: Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva. Eur J Oral Sci 2002;110:149–156.
  9. Carlén A, Olsson J: Monoclonal antibodies against a high-molecular weight agglutinin block adherence to experimental pellicles on hydroxyapatite and aggregation of Streptococcus mutans. J Dent Res 1995;74:1040–1047.
  10. Edgerton M, Koshlukova S, Araujo MWB, Patel RC, Dong J, Bruenn JA: Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob Agents Chemother 2000;44:3310–3316.
  11. Ericson T, Rundegren J: Characterization of a salivary agglutinin reacting with a serotype c strain of Streptococcus mutans. Eur J Biochem 1983;133:255–261.
  12. Faber C, Stallmann HP, Lyaruu DM, De Blieck JMA, Bervoets TJM, Nieuw Amerongen AV, Wuisman PIJM: Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads. J Antimicrob Chemother 2003;51:1359–1364.
  13. Groenink J, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Cationic amphipathic peptides, derived from bovine and human lactoferrins, with antimicrobial activity against oral pathogens. FEMS Microbiol Lett 1999;179:217–222.
  14. Gyurko C, Lendenmann U, Helmerhorst EJ, Troxler RF, Oppenheim FG: Killing of Candida albicans by histatin 5: Cellular uptake and energy requirement. Antonie Van Leeuwenhoek 2001;79:297–309.
  15. Helmerhorst EJ, van ’t Hof W, Breeuwer P, Veerman ECI, Abee T, Troxler RF, Nieuw Amerongen AV, Oppenheim FG: Characterization of histatin 5 with respect to amphipathicity, hydrophobicity, and effects on cell and mitochondrial membrane integrity excludes a candidacidal mechanism of pore formation. J Biol Chem 2001;276:5643–5649.
  16. Helmerhorst EJ, van ’t Hof W, Veerman ECI, Simoons-Smit AM, Nieuw Amerongen AV: Synthetic histatin analogs with broad-spectrum antimicrobial activity. Biochem J 1997;326:39–45.
  17. Helmerhorst EJ, Reijnders IM, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides against Candida albicans cells and human erythrocytes. FEBS Lett 1999;449:105–110.
  18. den Hertog AL, Wong Fong Sang HW, Kraayenhof R, Bolscher JGM, van’t Hof W, Veerman ECI, Nieuw Amerongen AV: Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization. Biochem J 2004, in press.
  19. van ’t Hof W, Veerman ECI, Helmerhorst EJ, Nieuw Amerongen AV: Antimicrobial peptides: Properties and applicability. Biol Chem 2001;382:597–619.
  20. Kolenbrander PE, London J: Adhere today, here tomorrow: Oral bacterial adherence. J Bacteriol 1993;175:3247–3252.
  21. van der Kraan MIA, Groenink J, Nazmi K, Veerman ECI, Bolscher JGM, Nieuw Amerongen AV: Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin. Peptides 2004, in press.
  22. Lamont RJ, Demuth DR, Davis CA, Malamud D, Rosan B: Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria. Infect Immun 1991;59:3446–3450.
  23. Levine MJ, Reddy MS, Tabak LA, Loomis RE, Bergey EJ, Jones PC, Cohen RE, Stinson MW, Al-Hashimi I: Structural aspects of salivary glycoproteins. J Dent Res 1987;66:436–441.
  24. Ligtenberg TJM, Bikker FJ, Groenink J, Tornoe I, Leth-Larsen R, Veerman ECI, Nieuw Amerongen AV, Holmskov U: Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340. Biochem J 2001;359:243–248.
  25. Ligtenberg AJM, Veerman ECI, Nieuw Amerongen AV: A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans. Antonie Van Leeuwenhoek 2000;77:21–30.
  26. Liu B, Rayment SA, Gyurko C, Oppenheim FG, Offner GD, Troxler RF: The recombinant N-terminal region of human salivary mucin MG2 (MUC7) contains a binding domain for oral Streptococci and exhibits candidacidal activity. Biochem J 2000;345:557–564.
  27. Loomis RE, Prakobphol A, Levine MJ, Reddy MS, Jones PC: Biochemical and biophysical comparison of two mucins from human submandibular-sublingual saliva. Arch Biochem Biophys 1987;258:452–464.
  28. MacKay BJ, Denepitiya L, Iacono VJ, Krost SB, Pollock JJ: Growth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutans. Infect Immun 1984;44:695–701.
  29. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB: Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun 1999;67:2740–2745.
  30. Mosca DA, Hurst MA, So W, Viajar BSC, Fujii CA, Falla TJ: IB-367, a protegrin peptide with in vitro and in vivo activities against the microflora associated with oral mucositis. Antimicrob Agents Chemother 2000;44:1803–1808.
  31. Murakami M, Ohtake T, Dorschner RA, Gallo RL: Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res 2002;81:845–850.
  32. Nieuw Amerongen AV, Bolscher JGM, Veerman ECI: Salivary mucins: Protective functions in relation to their diversity. Glycobiology 1995;5:733–740.
  33. Nieuw Amerongen AV, Oderkerk CH, Driessen AA: Role of mucins from human whole saliva in the protection of tooth enamel against demineralizatiuon in vitro. Caries Res 1987;21:297–309.
  34. Nieuw Amerongen AV, Veerman ECI: Saliva – the defender of the oral cavity. Oral Dis 2002;8:12–22.
  35. Paquette DW, Simpson DM, Friden P, Braman V, Williams RC: Safety and clinical effects of topical histatin gels in humans with experimental gingivitis. J Clin Periodontol 2002;29:1051–1058.
  36. Pollock JJ, Denepitiya L, MacKay BJ, Iacono V: Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans. Infect Immun 1984:44:702–707.
  37. Prakobphol A, Xu F, Hoang VM, Larsson T, Bergstrom J, Johansson I, Frangsmyr L, Holmskov U, Leffler H, Nilsson C, Boren T, Wright JR, Stromberg N, Fisher SJ: Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340. J Biol Chem 2000;275:39860–39866.
  38. van der Reijden WA, Veerman ECI, Nieuw Amerongen AV: Shear rate dependent viscoelastic behavior of human glandular salivas. Biorheology 1993;30:141–152.
  39. Rothstein DM, Spacciapoli P, Tran LT, Xu T, Roberts FD, Dalla Serra M, Buxton DK, Oppenheim FG, Friden P: Anticandida activity is retained in P-113, a 12-amino acid fragment of histatin 5. Antimicrob Agents Chemother 2001;45:1367–1373.
  40. Rudney JD, Hickey KL, Ji Z: Cumulative correlations of lysozyme, lactoferrin, peroxidase, S-IgA, amylase, and total protein concentrations with adherence of oral viridans streptococci to microplates coated with human saliva. J Dent Res 1999;78:759–768.
  41. Ruissen ALA, Groenink J, Helmerhorst EJ, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Effects of histatin 5 and derived peptides on Candida albicans. Biochem J 2001;356:361–368.
  42. Ruissen ALA, Groenink J, Krijtenberg P, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Internalisation and degradation of histatin 5 by Candida albicans. Biol Chem 2003;384:183–190.
  43. Sajjan US, Tran LT, Sole N, Rovaldi C, Akiyama A, Friden PM, Forstner JF, Rothstein DM: P-113D, an antimicrobial peptide active against Pseudomonas aeruginosa, retains activity in the presence of sputum from cystic fibrosis patients. Antimicrob Agents Chemother 2001;45:3437–3444.
  44. Sawaki K, Mizukawa N, Yamaai T, Fukunaga J, Sugahara T: Immunohistochemical study on expression of α-defensin and β-defensin-2 in human buccal epithelia with candidiasis. Oral Dis 2002;8:37–41.
  45. Sörensen OE, Follin P, Johnson AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N: Human cathelicidin, hCAP18, is processed to the antimicrobial peptide LL37 by extracellular cleavage with proteinase 3. Blood 2001;97:3951–3959.
  46. Thornton DJ, Khan N, Mehrotra R, Howard M, Veerman E, Packer NH, Sheehan JK: Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 1999;9:293–302.
  47. Veerman ECI, Bank CMC, Namavar F, Appelmelk BJ, Bolscher JGM, Nieuw Amerongen AV: Sulfated glycans on oral mucin as receptors for Helicobacter pylori. Glycobiology 1997a;7:737–743.
  48. Veerman ECI, Bolscher JGM, Appelmelk BJ, Bloemena E, van den Berg TK, Nieuw Amerongen AV: A monoclonal antibody directed against high Mr salivary mucins recognizes the SO3-3Galβ1-3GlcNAc moiety of sulfo-Lewisa: A histochemical survey of human and rat tissue. Glycobiology 1997b;7:37–43.
  49. Veerman ECI, van den Keijbus PAM, Nazmi K, Vos W, van der Wal JE, Bloemena E, Bolscher JGM, Nieuw Amerongen AV: Distinct localization of MUC5B glycoforms in the human salivary glands. Glycobiology 2003;13:363–366.
  50. Veerman ECI, Ligtenberg AJM, Schenkels LCPM, Walgreen-Weterings E, Nieuw Amerongen AV: Binding of human high-molecular-weight salivary mucins (MG1) to Hemophilus parainfluenzae. J Dent Res 1995;74:351–357.
  51. Woo JS, Jeong JY, Hwang YJ, Chae SW, Hwang SJ, Lee HM: Expression of cathelicidin in human salivary glands. Arch Otolaryngol Head Neck Surg 2003;129:211–214.

  

Author Contacts

Dr. A. van Nieuw Amerongen
Vrije Universiteit, Department of Oral Biochemistry
Van der Boechorststraat 7, NL–1081 BT Amsterdam (The Netherlands)
Tel. +31 20 4448675, Fax +31 20 4448685E-Mail a.van_nieuw_amerongen.obc.acta@med.vu.nl

  

Article Information

Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 2, Number of References : 51

  

Publication Details

Caries Research (Journal of the European Organization for Caries Research (ORCA))
Journal founded 1967 by Y. Ericsson; edited 1970–1987 by K.G. König; 1987–1994 by J.M. ten Cate; 1994–2000 by J. Tenovuo

Vol. 38, No. 3, Year 2004 (Cover Date: May-June 2004)

Journal Editor: R.P. Shellis, Bristol
ISSN: 0008–6568 (print), 1421–976X (Online)

For additional information: http://www.karger.com/journals/cre


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References

  1. Abiko Y, Jinbu Y, Noguchi T, Nishimura M, Kusano K, Amaratunga P, Shibata T, Kaku T: Upregulation of human β-defensin 2 peptide expression in oral lichen planus, leukoplakia and candidiasis: An immunohistochemical study. Pathol Res Pract 2002;198:537–542.
  2. Bergey EJ, Cho MI, Hammarskjold ML, Rekosh D, Levine MJ, Blumberg BM, Epstein LG: Aggregation of human-immunodeficiency-virus type-1 by human salivary secretions. Crit Rev Oral Biol Med 1993a;4:467–474.
  3. Bergey EJ, Gu M, Collins AR, Bradway SD, Levine MJ: Modulation of herpes-simplex virus type-1 replication by human salivary secretions. Oral Microbiol Immunol 1993b;8:89–93.
  4. Bikker FJ, Ligtenberg AJM, Nazmi K, Veerman ECI, van ’t Hof W, Bolscher JGM, Poustka A, Nieuw Amerongen AV, Mollenhauer J: Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily. J Biol Chem 2002a;277:32109–32115.
  5. Bikker FJ, Ligtenberg AJM, van der Wal JE, van den Keijbus PAM, Holskov U, Veerman ECI, Nieuw Amerongen AV: Immunohistochemical detection of salivary agglutinin/gp-340 in human parotid, submandibular, and labial salivary glands. J Dent Res 2002b;81;134–139.
  6. Bobek LA, Tsai H, Biesbrock AR, Levine MJ: Molecular-cloning, sequence, and specificity of expression of the gene encoding the low-molecular-weight human salivary mucin (MUC7). J Biol Chem 1993;268:20563–20569.
  7. Bolscher JGM, Groenink J, van der Kwaak JS, van den Keijbus PAM, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Detection and quantification of MUC7 in submandibular, sublingual, palatine, and labial saliva by anti-peptide antiserum. J Dent Res 1999;78:1362–1369.
  8. Bolscher JGM, Nazmi K, Ran LJ, Van Engelenburg FAC, Schuitemaker H, Veerman ECI, Nieuw Amerongen AV: Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva. Eur J Oral Sci 2002;110:149–156.
  9. Carlén A, Olsson J: Monoclonal antibodies against a high-molecular weight agglutinin block adherence to experimental pellicles on hydroxyapatite and aggregation of Streptococcus mutans. J Dent Res 1995;74:1040–1047.
  10. Edgerton M, Koshlukova S, Araujo MWB, Patel RC, Dong J, Bruenn JA: Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob Agents Chemother 2000;44:3310–3316.
  11. Ericson T, Rundegren J: Characterization of a salivary agglutinin reacting with a serotype c strain of Streptococcus mutans. Eur J Biochem 1983;133:255–261.
  12. Faber C, Stallmann HP, Lyaruu DM, De Blieck JMA, Bervoets TJM, Nieuw Amerongen AV, Wuisman PIJM: Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads. J Antimicrob Chemother 2003;51:1359–1364.
  13. Groenink J, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Cationic amphipathic peptides, derived from bovine and human lactoferrins, with antimicrobial activity against oral pathogens. FEMS Microbiol Lett 1999;179:217–222.
  14. Gyurko C, Lendenmann U, Helmerhorst EJ, Troxler RF, Oppenheim FG: Killing of Candida albicans by histatin 5: Cellular uptake and energy requirement. Antonie Van Leeuwenhoek 2001;79:297–309.
  15. Helmerhorst EJ, van ’t Hof W, Breeuwer P, Veerman ECI, Abee T, Troxler RF, Nieuw Amerongen AV, Oppenheim FG: Characterization of histatin 5 with respect to amphipathicity, hydrophobicity, and effects on cell and mitochondrial membrane integrity excludes a candidacidal mechanism of pore formation. J Biol Chem 2001;276:5643–5649.
  16. Helmerhorst EJ, van ’t Hof W, Veerman ECI, Simoons-Smit AM, Nieuw Amerongen AV: Synthetic histatin analogs with broad-spectrum antimicrobial activity. Biochem J 1997;326:39–45.
  17. Helmerhorst EJ, Reijnders IM, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides against Candida albicans cells and human erythrocytes. FEBS Lett 1999;449:105–110.
  18. den Hertog AL, Wong Fong Sang HW, Kraayenhof R, Bolscher JGM, van’t Hof W, Veerman ECI, Nieuw Amerongen AV: Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization. Biochem J 2004, in press.
  19. van ’t Hof W, Veerman ECI, Helmerhorst EJ, Nieuw Amerongen AV: Antimicrobial peptides: Properties and applicability. Biol Chem 2001;382:597–619.
  20. Kolenbrander PE, London J: Adhere today, here tomorrow: Oral bacterial adherence. J Bacteriol 1993;175:3247–3252.
  21. van der Kraan MIA, Groenink J, Nazmi K, Veerman ECI, Bolscher JGM, Nieuw Amerongen AV: Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin. Peptides 2004, in press.
  22. Lamont RJ, Demuth DR, Davis CA, Malamud D, Rosan B: Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria. Infect Immun 1991;59:3446–3450.
  23. Levine MJ, Reddy MS, Tabak LA, Loomis RE, Bergey EJ, Jones PC, Cohen RE, Stinson MW, Al-Hashimi I: Structural aspects of salivary glycoproteins. J Dent Res 1987;66:436–441.
  24. Ligtenberg TJM, Bikker FJ, Groenink J, Tornoe I, Leth-Larsen R, Veerman ECI, Nieuw Amerongen AV, Holmskov U: Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340. Biochem J 2001;359:243–248.
  25. Ligtenberg AJM, Veerman ECI, Nieuw Amerongen AV: A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans. Antonie Van Leeuwenhoek 2000;77:21–30.
  26. Liu B, Rayment SA, Gyurko C, Oppenheim FG, Offner GD, Troxler RF: The recombinant N-terminal region of human salivary mucin MG2 (MUC7) contains a binding domain for oral Streptococci and exhibits candidacidal activity. Biochem J 2000;345:557–564.
  27. Loomis RE, Prakobphol A, Levine MJ, Reddy MS, Jones PC: Biochemical and biophysical comparison of two mucins from human submandibular-sublingual saliva. Arch Biochem Biophys 1987;258:452–464.
  28. MacKay BJ, Denepitiya L, Iacono VJ, Krost SB, Pollock JJ: Growth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutans. Infect Immun 1984;44:695–701.
  29. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB: Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun 1999;67:2740–2745.
  30. Mosca DA, Hurst MA, So W, Viajar BSC, Fujii CA, Falla TJ: IB-367, a protegrin peptide with in vitro and in vivo activities against the microflora associated with oral mucositis. Antimicrob Agents Chemother 2000;44:1803–1808.
  31. Murakami M, Ohtake T, Dorschner RA, Gallo RL: Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res 2002;81:845–850.
  32. Nieuw Amerongen AV, Bolscher JGM, Veerman ECI: Salivary mucins: Protective functions in relation to their diversity. Glycobiology 1995;5:733–740.
  33. Nieuw Amerongen AV, Oderkerk CH, Driessen AA: Role of mucins from human whole saliva in the protection of tooth enamel against demineralizatiuon in vitro. Caries Res 1987;21:297–309.
  34. Nieuw Amerongen AV, Veerman ECI: Saliva – the defender of the oral cavity. Oral Dis 2002;8:12–22.
  35. Paquette DW, Simpson DM, Friden P, Braman V, Williams RC: Safety and clinical effects of topical histatin gels in humans with experimental gingivitis. J Clin Periodontol 2002;29:1051–1058.
  36. Pollock JJ, Denepitiya L, MacKay BJ, Iacono V: Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans. Infect Immun 1984:44:702–707.
  37. Prakobphol A, Xu F, Hoang VM, Larsson T, Bergstrom J, Johansson I, Frangsmyr L, Holmskov U, Leffler H, Nilsson C, Boren T, Wright JR, Stromberg N, Fisher SJ: Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340. J Biol Chem 2000;275:39860–39866.
  38. van der Reijden WA, Veerman ECI, Nieuw Amerongen AV: Shear rate dependent viscoelastic behavior of human glandular salivas. Biorheology 1993;30:141–152.
  39. Rothstein DM, Spacciapoli P, Tran LT, Xu T, Roberts FD, Dalla Serra M, Buxton DK, Oppenheim FG, Friden P: Anticandida activity is retained in P-113, a 12-amino acid fragment of histatin 5. Antimicrob Agents Chemother 2001;45:1367–1373.
  40. Rudney JD, Hickey KL, Ji Z: Cumulative correlations of lysozyme, lactoferrin, peroxidase, S-IgA, amylase, and total protein concentrations with adherence of oral viridans streptococci to microplates coated with human saliva. J Dent Res 1999;78:759–768.
  41. Ruissen ALA, Groenink J, Helmerhorst EJ, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Effects of histatin 5 and derived peptides on Candida albicans. Biochem J 2001;356:361–368.
  42. Ruissen ALA, Groenink J, Krijtenberg P, Walgreen-Weterings E, van ’t Hof W, Veerman ECI, Nieuw Amerongen AV: Internalisation and degradation of histatin 5 by Candida albicans. Biol Chem 2003;384:183–190.
  43. Sajjan US, Tran LT, Sole N, Rovaldi C, Akiyama A, Friden PM, Forstner JF, Rothstein DM: P-113D, an antimicrobial peptide active against Pseudomonas aeruginosa, retains activity in the presence of sputum from cystic fibrosis patients. Antimicrob Agents Chemother 2001;45:3437–3444.
  44. Sawaki K, Mizukawa N, Yamaai T, Fukunaga J, Sugahara T: Immunohistochemical study on expression of α-defensin and β-defensin-2 in human buccal epithelia with candidiasis. Oral Dis 2002;8:37–41.
  45. Sörensen OE, Follin P, Johnson AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N: Human cathelicidin, hCAP18, is processed to the antimicrobial peptide LL37 by extracellular cleavage with proteinase 3. Blood 2001;97:3951–3959.
  46. Thornton DJ, Khan N, Mehrotra R, Howard M, Veerman E, Packer NH, Sheehan JK: Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 1999;9:293–302.
  47. Veerman ECI, Bank CMC, Namavar F, Appelmelk BJ, Bolscher JGM, Nieuw Amerongen AV: Sulfated glycans on oral mucin as receptors for Helicobacter pylori. Glycobiology 1997a;7:737–743.
  48. Veerman ECI, Bolscher JGM, Appelmelk BJ, Bloemena E, van den Berg TK, Nieuw Amerongen AV: A monoclonal antibody directed against high Mr salivary mucins recognizes the SO3-3Galβ1-3GlcNAc moiety of sulfo-Lewisa: A histochemical survey of human and rat tissue. Glycobiology 1997b;7:37–43.
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