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8 Speekselmucinen: bescherming van alle orale weefsels

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Samenvatting

Kenmerkend voor humaan totaalspeeksel is de aanwezigheid van twee soorten mucinen: het hoogmoleculaire (MUC5B = MG-1) en het laagmoleculaire (MUC7 = MG-2) mucine. MUC5B is afkomstig uit alle (sero)muceuze speekselklieren. MUC7 lijkt niet in alle personen aanwezig te zijn in palatinaal speeksel. Beide soorten mucinen verschillen in biochemische eigenschappen en hebben waarschijnlijk verschillende functies.

MUC5B is verantwoordelijk voor de visco-elastische eigenschappen van speeksel en speelt een belangrijke rol bij de lubricatie (Stokes en Davies, 2007). MUC5B bindt sterk aan tandglazuur en kan dan ook worden beschouwd als een tandpelliclecomponent. In die hoedanigheid beschermt MUC5B de gebitselementen tegen demineralisatie door zuuraanvallen. MUC5B bindt niet aan de meest voorkomende orale bacteriën. Alleen Haemophilus (para)influenzae en Helicobacter pylori zijn in staat MUC5B te binden.

MUC7 bindt echter aan het merendeel van de orale micro-organismen en kan deze met medewerking van S-IgA doen aggregeren. Beide mucinen kunnen door micro-organismen gebruikt worden als voedingssubstraat. Vooral eindstandige siaalzuurresiduen worden in de mondholte snel afgesplitst door bacterieel sialidase/neuraminidase, vooral bij slechte mondhygiëne.

Humane speekselmucinen verschillen sterk van alle bekende dierlijke speekselmucinen. Met name de koolhydraatketens zijn complexer en meer heterogeen. In het algemeen blijkt dat de speekselmucinen een vitale rol spelen bij het gezond houden van zowel de gebitselementen als de mucosale weefsels. Zij beschermen alle orale weefseloppervlakken tegen mechanische beschadiging, zuurinwerking en proteolytische afbraak door micro-organismen.

Literatuur

  1. Allen A. en G. Flemström. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am. J. Physiol. Cell Physiol. 288, (2005)C1–C19.PubMedCrossRefGoogle Scholar
  2. Baughan L.W., F.J. Robertello, D.C. Sarrett, P.A. Denny en P.C. Denny. Salivary mucin as related to oral Streptococcus mutans in elderly people. Oral Microbiol. Immunol. 15, (2000)10–14.PubMedCrossRefGoogle Scholar
  3. Becerra L., R.V. Soares, L.S. Bruno, C.C. Siqueira, F.G. Oppenheim, G.D. Offner, e.a. Patterns of secretion of mucins and non-mucin glycoproteins in human submandibular/sublingual secretion. Archs Oral Biol. 48, (2003)147–154.CrossRefGoogle Scholar
  4. Bergey E.J., M.I. Cho, B.M. Blumberg, M.-L. Hammarskjøld, D. Rekosh, L.G. Epstein, e.a. Interaction of HIV-1 and human salivary mucins. J. Acquired Imun. Def. Syndrome 7, (1994)995–1002.Google Scholar
  5. Biesbrock A.R., L.A. Bobek en M.J. Levine. MUC7 gene expression and genetic polymorphism. Glycoconjugate J. 14, (1997)415–422.CrossRefGoogle Scholar
  6. Bobek L.A., L. Liu, S.N.J. Sait, T.B. Shows, Y.A. Bobek en M.J. Levine. Structure and chromosomal localization of the human salivary gene, MUC7. Genomics 31, (1996) 277–282.PubMedCrossRefGoogle Scholar
  7. Bobek L.A., M. Li, N. Rojstaczer, C. Jones, K.W. Gross en M.J. Levine. Tissue-specific expression of human salivary mucin gene, MUC7, in transgenic mice. Transgenic Res. 7, (1998)195–204.PubMedCrossRefGoogle Scholar
  8. Bobek L.A. en H. Situ. MUC7 20-mer: investigation of antimicrobial activity, secondary structure, and possible mechanism of antifungal action. Antimicrob. Agents Chemother. 47, (2003)643–652.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Bolscher J., E. Veerman, A. van Nieuw Amerongen, A. Tulp en D. Verwoerd. Distinct populations of high-Mr mucins secreted by different human salivary glands discriminated by density-gradient electrophoresis. Biochem. J. 309, (1995)801–806.PubMedCentralPubMedGoogle Scholar
  10. Bolscher J.G.M., J. Groenink, J.S. van der Kwaak, P.A.M. van den Keijbus, W.van ’t Hof, E.C.I. Veerman, e.a. Detection and quantification of MUC7 in submandibular, sublingual, palatine and labial saliva by anti-peptide antiserum. J. Dent. Res. 78, (1999)1362–1369.PubMedCrossRefGoogle Scholar
  11. Bongaerts J.H.H., D. Rossetti en J.R. Stokes. The lubricating properties of human whole saliva. Tribol. Lett. 27, (2007) 277–287.CrossRefGoogle Scholar
  12. Bosch J.A., E.J.C. de Geus, T.J.M. Ligtenberg, K. Nazmi, E.C.I. Veerman, J. Hoogstraten, e.a. Salivary MUC5B-mediated adherence (ex vivo) of Helicobacter pylori during acute stress. Psychosom. Med. 62, (2000)40–49.PubMedCrossRefGoogle Scholar
  13. Bradway S.D., E.J. Bergey, F.A. Scannapieco, N. Ramasubbu, S. Zawacki en M.J. Levine. Formation of salivary-mucosal pellicle: the role of transglutaminase. Biochem. J. 284, (1992) 557–564.PubMedCentralPubMedGoogle Scholar
  14. Cardenas M., U. Elofsson en L. Lindh. Salivary mucin MUC5B could be an important component of in vitro pellicles of human saliva: An in situ ellipsometry and atomic force microscopy study. Biomacromolecules 8, (2007)1149–1156.PubMedCrossRefGoogle Scholar
  15. Gipson I.K. Mucins of the human endocervix. Front. Biosci. 6,(2001)d1245–1255.PubMedCrossRefGoogle Scholar
  16. Groenink J., A.J.M. Ligtenberg, E.C.I. Veerman, J.G.M. Bolscher en A. van Nieuw Amerongen. Interaction of the salivary low-molecular-weight mucin (MG2) with Actinobacillus actinomycetemcomitans. Ant. Van Leeuwenh. 70, (1996)79–87CrossRefGoogle Scholar
  17. Groenink J., E. Walgreen-Weterings, K. Nazmi, J.G.M. Bolscher, E.C.I. Veerman, A.J. van Winkelhoff, e.a. Salivary lactoferrin and low-Mr mucin MG2 in Actinobacillus actinomycetemcomitans-associated periodontitis. J. Clin. Periodontol. 26, (1999)269–275.PubMedCrossRefGoogle Scholar
  18. Gururaja T.L., N. Ramasubbu, P. Venugopalan, M.S. Reddy, K. Ramalingam en M.J. Levine. Structural features of the human salivary mucin, MUC7. Glycoconjugate J. 15, (1998)457–467.CrossRefGoogle Scholar
  19. Gururaja T.L., M.J. Levine, D.T. Tran, G.A. Naganagowda, K. Ramalingam, N. Ramasubbu, e.a. Candidacidal activity prompted by N-terminus histatin- like domain of human salivary mucin (MUC7). Biochim. Biophys. Acta 1431, (1999)107–119.PubMedCrossRefGoogle Scholar
  20. Iontcheva I., F.G. Oppenheim en R.F. Troxler. Human salivary mucin MG1 selectively forms heterotypic complexes with amylase, PRPs, statherin and with histatins. J. Dent. Res. 76, (1997)734–743.PubMedCrossRefGoogle Scholar
  21. Kesimer M. en J.K. Sheehan. Analyzing the functions of large glycoconjugates through the dissipative properties of their absorbed layers using the gelforming mucin MUC5B as an example. Glycobiology 18, (2008)463–472.PubMedCrossRefGoogle Scholar
  22. Kim W., Y.K. Kim, S.C. Chung, S.W. Lee en H.S. Kho. Detection of ABH blood group antigens in the saliva of Koreans and their stability according to storage of saliva samples. For. Sci. Int. 129, (2002)58–63.Google Scholar
  23. Kirkbride H.J., J.G. Bolscher, K. Nazmi, L.E. Vinall, M.W. Nash, F.M. Moss, e.a. Genetic polymorphism of MUC7: allele frequencies and association with asthma. Eur. J. Human Genetics 9, (2001)347–354.CrossRefGoogle Scholar
  24. Kirkham S., J.K. Sheehan, D. Knight, P.S. Richardson en D.J. Thornton. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem. J. 361, (2002)537–546.PubMedCentralPubMedCrossRefGoogle Scholar
  25. Lamblin G., S. Degroote, J.-M. Perini, P. Delmotte, A. Scharfman, M. Davril, e.a. Human airway mucin glycosylation: A combinatory of carbohydrate determinants which vary in cystic fibrosis. Glycoconjugate J. 18, (2001)661–684.CrossRefGoogle Scholar
  26. Levine M.J., M.S. Reddy, L.A. Tabak, R.E. Loomis, E.J. Bergey, P.C. Jones, e.a. Structural aspects of salivary glycoproteins. J. Dent. Res. 66, (1987) 436–441.PubMedCrossRefGoogle Scholar
  27. Li S.M. en L.A. Bobek. Functional analysis of human MUC7 mucin gene 5’-flanking region in lung epithelial cells. Am. J. Respir. Cell Mol. Biol. 35, (2006)593–601.PubMedCentralPubMedCrossRefGoogle Scholar
  28. Ligtenberg A.J.M., E. Walgreen-Weterings, E.C.I. Veerman, J.J. de Soet, J. de Graaff en A. van Nieuw Amerongen. Influence of saliva on aggregation and adherence of Streptococcus gordonii HG 222. Infect. Immun. 60, (1992)3878–3884.PubMedCentralPubMedGoogle Scholar
  29. Linden S., J.Mahdavi, C. Semino-Mora, C. Olsen, I. Carlstedt, T. Boren, e.a. Role of ABO secretor statusin mucosal innate immunity and H. pylori infection. PLOS pathogens 4, (2008)6–13.CrossRefGoogle Scholar
  30. Liu B., S.A. Rayment, R.V. Soares, F.G. Oppenheim, G.D. Offner, P. Fives-Taylor, e.a. Interaction of human salivary mucin MG2, its recombinant N-terminal region and a synthetic peptide with Actinobacillus actinomycetemcomitans. J. Periodont. Res. 37, (2002)416–424.PubMedCrossRefGoogle Scholar
  31. Milne R.W. en C. Dawes. The relative contributions of different salivary glands to the blood group activity of whole saliva in humans. Vox Sang. 25, (1973)298–307.PubMedCrossRefGoogle Scholar
  32. Nielsen P.A., U. Mandel, M.H. Therkildsen en H. Clausen. Differential expression of human high molecular weight mucin (MG1) and low molecular weight salivary mucin (MG2). J. Dent. Res. 75, (1996)1820–1826.PubMedCrossRefGoogle Scholar
  33. Nielsen P.A., E.P. Bennett, H.H. Wandall, M.H. Therkildsen, J. Hannibal en H. Clausen. Identification of a major human high molecular weight salivary mucin (MG1) as tracheobronchial mucin MUC5B. Glycobiology 7, (1997)413–419.PubMedCrossRefGoogle Scholar
  34. Nieuw Amerongen A. van, C.H. Oderkerk en P.A. Roukema. Role of mucins from human whole saliva in the protection of tooth enamel against demineralization in vitro. Caries Res. 21, (1987)297–309.CrossRefGoogle Scholar
  35. Nieuw Amerongen A. van en E.C.I. Veerman. Speeksel, een onderschat secreet. Natuur en Techniek 61, (1993)568–579.Google Scholar
  36. Nieuw Amerongen A. van, J.G.M. Bolscher en E.C.I. Veerman. Salivary mucins: Protective functions in relation to their diversity. Glycobiology 5, (1995)733–740.CrossRefGoogle Scholar
  37. Nieuw Amerongen A. van, J.G.M. Bolscher, E. Bloemena en E.C.I. Veerman. Sulfomucins in the human body. Biol. Chem. 379, (1998)1–18.PubMedCrossRefGoogle Scholar
  38. Ogasawara A., N. Komaki, H. Akai, K. Hori, H. Watanabe, T. Watanabe, e.a. Hyphal formation of Candida albicans is inhibited by salivary mucin. Biol. Pharm. Bull. 30, (2007)284–286.PubMedCrossRefGoogle Scholar
  39. Ohmori T., H. Toyoda, T. Toida, T. Imanari en H. Sato. Comparison of oligosaccharides derived from salivary mucin of Japanese secretor and non-secretor individuals of blood group type-A. Glycoconjugate J. 18, (2001)635–640.CrossRefGoogle Scholar
  40. Piludu M., S.A. Rayment, B. Liu, G.D. Offner, F.G. Oppenheim, R.F. Troxler, e.a. Electron microscopic immunogold localization of salivary mucins MG1 andMG2 in human submandibular and sublingual glands. J. Histochem. Cytochem. 51, (2003)69–79.CrossRefGoogle Scholar
  41. Prakobphol A., T. Borén, W. Ma, P. Zhixiang en S.J. Fisher. Highly glycosylated human salivary molecules present oligosaccharides that mediate adhesion of leukocytes and Helicobacter pylori. Biochemistry 44, (2005)2216–2224.PubMedCrossRefGoogle Scholar
  42. Rayment S.A., B. Liu, G.D. Offner, F.G. Oppenheim en R.F. Troxler. Immunoquantification of human salivary mucinsMG1 and MG2 in stimulated whole saliva: factors influencing mucin levels. J. Dent. Res. 79, (2000)1765–1772.PubMedCrossRefGoogle Scholar
  43. Reijden W.A. van der, E.C.I. Veerman en A. van Nieuw Amerongen. Speeksel en speekselsubstituten. Ned. Tijdschr. Tandh. 100, (1993)351–354.Google Scholar
  44. Retz M., J. Lehmann, E. Amann, B. Wullich, C. Röder en M. Stöckle. Mucin 7 and cytokeratin 20 as new diagnostic urinary markers for bladder tumor. J. Urology 169, (2003)86–89.CrossRefGoogle Scholar
  45. Roussel P. en P. Delmotte. The diversity of epithelial secreted mucins. Curr. Organic Chem. 8, (2004)413–437.CrossRefGoogle Scholar
  46. Sandberg T., J. Carlsson en M. Karlsson. Mucin coatings suppress neutrophil adhesion to a polymeric model biomaterial. Microsc. Res. Techn. 70, (2007)864–868CrossRefGoogle Scholar
  47. Satyanarayana J., T.L. Gururaja, G.A. Naganagowda en M.J. Levine. Synthesis and conformational features of human salivary mucin C-terminal derived peptide epitope carrying Thomsen-Friedenreich antigen:implications for its role in self-association. Biopolymers 58, (2001)500–510.PubMedCrossRefGoogle Scholar
  48. Schenkels L.C.P.M., E.C.I. Veerman en A. van Nieuw Amerongen. Biochemical composition of human saliva in relation to other mucosal fluids. Crit. Rev. Oral Biol. Med. 6, (1995)161–175.PubMedCrossRefGoogle Scholar
  49. Schipper R.G., E. Siletti en M.H. Vingerhoeds. Saliva as research material: Biochemical, physicochemical and practical aspects. Archs Oral Biol. 52, (2007)1114–1135.CrossRefGoogle Scholar
  50. Soares R.V., B. Liu, F.G. Oppenheim, G. Offner en R.F. Troxler. Structural characterisation of cysteines in a bacterial-binding motif of human salivary mucin MG2. Archs Oral Biol. 47, (2002)591–597.CrossRefGoogle Scholar
  51. Soares R.V., C.C. Siqueira, L.S. Bruno, F.G. Oppenheim, G.D. Offner en R.F. Troxler. MG2 and lactoferrin form a heterotypic complex in salivary secretions. J. Dent. Res. 82, (2003)471–475.PubMedCrossRefGoogle Scholar
  52. Sonesson M., C. Wickström, B. Kinnby, D. Ericson en L. Matsson. Mucins MUC5B and MUC7 in minor salivary gland secretion of children and adults. Archs Oral Biol. 53, (2008)523–527.CrossRefGoogle Scholar
  53. Stokes J.R. en G.A. Davies. Viscoelasticity of human whole saliva collected after acid and mechanical stimulation. Biorheology 44, (2007)141–160.PubMedGoogle Scholar
  54. Strous G.J. en J. Dekker. Mucin-type glycoproteins. Crit. Rev. Biochem. Mol. Biol. 27, (1992)57–92.PubMedCrossRefGoogle Scholar
  55. Tabak L.A. Genetic control of salivary mucin formation. In: Frontiers of Oral Biology 8, (1991) 77–94.Google Scholar
  56. Tabak L.A. In defense of the oral cavity: structure, biosynthesis and function of salivary mucins. Ann. Rev. Physiol. 57, (1995)547–564.CrossRefGoogle Scholar
  57. Thomsson K.A., A. Prakobphol, H. Leffler, M.S. Reddy, M.J. Levine, S.J. Fisher, e.a. The salivary mucin MG1 (MUC5B) carries a repertoire of unique oligosaccharides that is large and diverse. Glycobiology 12, (2002)1–14.PubMedCrossRefGoogle Scholar
  58. Toribara, J.R. Gum, P.J. Culhane, J.W. Lagace, J.W. Hicks, G.M. Petersen, e.a. MUC-2 human small intestinal N.W. mucin gene structure. J. Clin. Invest. 88, (1991)1005–1013.PubMedCentralPubMedCrossRefGoogle Scholar
  59. Veerman E.C.I., P.A.M. van den Keijbus, M. Valentijn-Benz en A. van Nieuw Amerongen. Isolation of different high-Mr mucin species from human whole saliva. Biochem. J. 283, (1992)807–811.PubMedCentralPubMedGoogle Scholar
  60. Veerman E.C.I., A.J.M. Ligtenberg, L.C.P.M. Schenkels, E. Walgreen-Weterings en A. van Nieuw Amerongen. Binding of human high-molecularweight salivary mucins (MG1) to Haemophilus parainfluenzae. J. Dent. Res. 74, (1995)351–357.PubMedCrossRefGoogle Scholar
  61. Veerman E.C.I., C.M.C. Bank, F. Namavar, B.J. Appelmelk, J.G.M. Bolscher en A. van Nieuw Amerongen. Sulfated glycans on oral mucin as receptors for Helicobacter pylori. Glycobiology 7, (1997)737–740.PubMedCrossRefGoogle Scholar
  62. Wei G.-X. en L.A. Bobek. Human salivary mucin MUC7 12-mer-L and 12-mer-D peptides: antifungal activity in saliva, enhancement of activity with protease inhibitor cocktail or EDTA, and cytotoxicity to human cells. Antimicrob. Agents Chemother. 49, (2005)2336–2342.PubMedCentralPubMedCrossRefGoogle Scholar
  63. Wei G.-X., A.N. Campagna en L.A. Bobek. Effect of MUC7 peptides on the growth of bacteria and on Streptococcus mutans biofilm. J. Antimicrob. Chemother. 57, (2006)1100–1109.PubMedCrossRefGoogle Scholar
  64. Wickström C., C. Christersson, J.R. Davies en I. Carlstedt. Macromolecular organization of saliva: identification of ‘insoluble’ MUC5B assemblies and non-mucin proteins in the gel phase. Biochem. J. 351, 2000)421–428.PubMedCentralPubMedCrossRefGoogle Scholar
  65. Wu A.M., G. Csako en A. Herp. Structure, biosynthesis and function of salivary mucins. Mol. Cell. Biochem. 137, (1994)39–55.PubMedCrossRefGoogle Scholar
  66. Zussman E., A.L. Yarin en R.M. Nagler. Age- and flow-dependency of salivary viscoelasticity. J. Dent. Res. 86, (2007)281–285.PubMedCrossRefGoogle Scholar

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© Bohn Stafleu van Loghum 2008

Authors and Affiliations

  1. 1.Sectie Orale BiochemieAcademisch Centrum Tandheelkunde Amsterdam (ACTA), Vrije Universiteit en Universiteit van AmsterdamAmsterdam

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