Human colonic mucus is a reservoir for antimicrobial peptides

Journal of Crohn's and Colitis

Volumn 7, Issue 12, 2013, Pages

  Antoni, Lena ^a   Nuding, Sabine ^a   Weller, Dagmar ^a   Gersemann, Michael ^b   Ott, German ^b   Wehkamp, Jan ^a,b   Stange, Eduard F ^b  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b ROBERT BOSCH HOSPITAL   (Germany)

Author keywords

Antimicrobial peptides; ; Inflammatory bowel disease; ; Large intestine; Mucus;

Indexed keywords

ADENOSINE PHOSPHATE; BETA DEFENSIN 1; BETA DEFENSIN 3; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; HISTONE; LYSOZYME; MUCIN; UBIQUITIN;

ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIUM ADHERENCE; COLON MUCOSA; EPITHELIUM; HUMAN; IMMUNOHISTOCHEMISTRY; LARGE INTESTINE; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; NUCLEOSOME; PRIORITY JOURNAL; QUALITATIVE RESEARCH; RESERVOIR; WESTERN BLOTTING;

AMP; ANTIMICROBIAL PEPTIDE; ANTIMICROBIAL PEPTIDES;; ELLA; ENZYME-LINKED LECTIN ASSAY; HIGH MOBILITY GROUP NUCLEOSOME-BINDING DOMAIN-CONTAINING PROTEIN 2; HMGN2; INFLAMMATORY BOWEL DISEASE;; LARGE INTESTINE; MALDI-TOF-MS; MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME-OF-FLIGHT MASS SPECTROMETRY; MUCUS;; REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; RP-HPLC;

ANTI-INFECTIVE AGENTS; BACTEROIDES FRAGILIS; CANDIDA ALBICANS; CATHELICIDINS; DEFENSINS; ENTEROCOCCUS FAECALIS; ESCHERICHIA COLI; FLOW CYTOMETRY; HISTONES; HMGN2 PROTEIN; HUMANS; INTESTINAL MUCOSA; MICROBIAL SENSITIVITY TESTS; MUCINS; MUCUS; MURAMIDASE; PEPTIDES; RECTUM; RIBOSOMAL PROTEINS; STAPHYLOCOCCUS AUREUS; UBIQUITIN;

EID: 84887616845     PISSN: 18739946     EISSN: 18764479     Source Type: Journal    
DOI: 10.1016/j.crohns.2013.05.006     Document Type: Article

References (53)

1. Wehkamp J., Koslowski M., Wang G., Stange E.F. Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic Crohn's disease. Mucosal Immunol 2008, 1(Suppl. 1):S67-S74. [PubMed: 19079235].
2. Müller C.A., Autenrieth I.B., Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 2005, 62:1297-1307. [PubMed: 15971105].
3. Hansson G.C., Johansson M.E. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Gut Microbes 2010, 1:51-54. [PubMed: 21327117].
4. Guaní-Guerra E., Santos-Mendoza T., Lugo-Reyes S.O., Terán L.M. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol 2010, 135:1-11. [PubMed: 20116332].
5. Jenssen H., Hamill P., Hancock R.E. Peptide antimicrobial agents. Clin Microbiol Rev 2006, 19:491-511. [PubMed: 16847082].
6. Jäger S., Stange E.F., Wehkamp J. Antimicrobial peptides in gastrointestinal inflammation. Int J Inflamm 2010, 2010:910283. [PubMed: 21151692].
7. Hazlett L., Wu M. Defensins in innate immunity. Cell Tissue Res 2011, 343:175-188. [PubMed: 20730446].
8. Bevins C.L., Salzman N.H. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011, 9:356-368. [PubMed: 21423246].
9. Harder J., Bartels J., Christophers E., Schröder J.M. A peptide antibiotic from human skin. Nature 1997, 387:861. [PubMed: 9202117].
10. Harder J., Bartels J., Christophers E., Schröder J.M. Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 2001, 276:5707-5713. [PubMed: 11085990].
11. O'Neil D.A., Porter E.M., Elewaut D., Anderson G.M., Eckmann L., Ganz T., et al. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999, 163:6718-6724. [PubMed: 10586069].
12. Wehkamp J., Fellermann K., Herrlinger K.R., Bevins C.L., Stange E.F. Mechanisms of disease: defensins in gastrointestinal diseases. Nat Clin Pract Gastroenterol Hepatol 2005, 2:406-415. [PubMed: 16265431].
13. Harder J., Gläser R., Schröder J.M. Human antimicrobial proteins effectors of innate immunity. J Endotoxin Res 2007, 13:317-338. [PubMed: 18182460].
14. Kawasaki H., Iwamuro S. Potential roles of histones in host defense as antimicrobial agents. Infect Disord Drug Targets 2008, 8:195-205. [PubMed: 18782037].
15. Fahlgren A., Hammarström S., Danielsson Å., Hammarström M.L. Beta-defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin Exp Immunol 2004, 137:379-385. [PubMed: 15270856].
16. Wehkamp J., Harder J., Weichenthal M., Mueller O., Herrlinger K.R., Fellermann K., et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003, 9:215-223. [PubMed: 12902844].
17. Howell S.J., Wilk D., Yadav S.P., Bevins C.L. Antimicrobial polypeptides of the human colonic epithelium. Peptides 2003, 24:1763-1770. [PubMed: 15019208].
18. Tollin M., Bergman P., Svenberg T., Jörnvall H., Gudmundsson G.H., Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 2003, 24:523-530. [PubMed: 12860195].
19. Allen A., Hutton D.A., Pearson J.P. The MUC2 gene product: a human intestinal mucin. Int J Biochem Cell Biol 1998, 30:797-801. [PubMed: 9722984].
20. Atuma C., Strugala V., Allen A., Holm L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol 2001, 280:G922-G929. [PubMed: 11292601].
21. Johansson M.E., Phillipson M., Petersson J., Velcich A., Holm L., Hansson G.C. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A 2008, 105:15064-15069. [PubMed: 18806221].
22. Moran A.P., Gupta A., Joshi L. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 2011, 60:1412-1425. [PubMed: 21228430].
23. Tytgat K.M., Büller H.A., Opdam F.J., Kim Y.S., Einerhand A.W., Dekker J. Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin. Gastroenterology 1994, 107:1352-1363. [PubMed: 7926500].
24. Van der Sluis M., De Koning B.A., De Bruijn A.C., Velcich A., Meijerink J.P., Van Goudoever J.B., et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006, 131:117-129. [PubMed: 16831596].
25. Larsson J.M., Karlsson H., Sjövall H., Hansson G.C. A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. Glycobiology 2009, 19:756-766. [PubMed: 19321523].
26. Pearson J.P., Brownlee I.A. The interaction of large bowel microflora with the colonic mucus barrier. Int J Inflamm 2010, 2010:321426. [PubMed: 21152122].
27. Meyer-Hoffert U., Hornef M.W., Henriques-Normark B., Axelsson L.G., Midtvedt T., Pütsep K., et al. Secreted enteric antimicrobial activity localises to the mucus surface layer. Gut 2008, 57:764-771. [PubMed: 18250125].
28. Nuding S., Fellermann K., Wehkamp J., Mueller H.A., Stange E.F. A flow cytometric assay to monitor antimicrobial activity of defensins and cationic tissue extracts. J Microbiol Methods 2006, 65:335-345. [PubMed: 16182394].
29. Felgentreff K., Beisswenger C., Griese M., Gulder T., Bringmann G., Bals R. The antimicrobial peptide cathelicidin interacts with airway mucus. Peptides 2006, 27:3100-3106. [PubMed: 16963160].
30. Gersemann M., Becker S., Kübler I., Koslowski M., Wang G., Herrlinger K.R., et al. Differences in goblet cell differentiation between Crohn's disease and ulcerative colitis. Differentiation 2009, 77:84-94. [PubMed: 19281767].
31. Shirazi T., Longman R.J., Corfield A.P., Probert C.S. Mucins and inflammatory bowel disease. Postgrad Med J 2000, 76:473-478. [PubMed: 10908374].
32. Phillipson M., Johansson M.E., Henriksnäs J., Petersson J., Gendler S.J., Sandler S., et al. The gastric mucus layers: constituents and regulation of accumulation. Am J Physiol Gastrointest Liver Physiol 2008, 295:G806-G812. [PubMed: 18719000].
33. Kim H.S., Cho J.H., Park H.W., Yoon H., Kim M.S., Kim S.C. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol 2002, 168:2356-2364. [PubMed: 11859126].
34. Li G.H., Mine Y., Hincke M.T., Nys Y. Isolation and characterization of antimicrobial proteins and peptide from chicken liver. J Pept Sci 2007, 13:368-378. [PubMed: 17431854].
35. Kieffer A.E., Goumon Y., Ruh O., Chasserot-Golaz S., Nullans G., Gasnier C., et al. The N- and C-terminal fragments of ubiquitin are important for the antimicrobial activities. FASEB J 2003, 17:776-778. [PubMed: 12594174].
36. Yoshio H., Tollin M., Gudmundsson G.H., Lagercrantz H., Jornvall H., Marchini G., et al. Antimicrobial polypeptides of human vernix caseosa and amniotic fluid: implications for newborn innate defense. Pediatr Res 2003, 53:211-216. [PubMed: 12538777].
37. Cole A.M., Liao H.I., Stuchlik O., Tilan J., Pohl J., Ganz T. Cationic polypeptides are required for antibacterial activity of human airway fluid. J Immunol 2002, 169:6985-6991. [PubMed: 12471133].
38. Fahlgren A., Hammarström S., Danielsson Å., Hammarström M.L. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol 2003, 131:90-101. [PubMed: 12519391].
39. Wehkamp J., Chu H., Shen B., Feathers R.W., Kays R.J., Lee S.K., et al. Paneth cell antimicrobial peptides: topographical distribution and quantification in human gastrointestinal tissues. FEBS Lett 2006, 580:5344-5350. [PubMed:16989824].
40. Ming L., Xiaoling P., Yan L., Lili W., Qi W., Xiyong Y., et al. Purification of antimicrobial factors from human cervical mucus. Hum Reprod 2007, 22:1810-1815. [PubMed: 17513850].
41. Hiemstra P.S., van den Barselaar M.T., Roest M., Nibbering P.H., van Furth R. Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages. J Leukoc Biol 1999, 66:423-428. [PubMed: 10496312].
42. Oren Z., Lerman J.C., Gudmundsson G.H., Agerberth B., Shai Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 1999, 341:501-513. [PubMed: 10417311].
43. Schroeder B.O., Wu Z., Nuding S., Groscurth S., Marcinowski M., Beisner J., et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature 2011, 469:419-423. [Pubmed: 21248850].
44. Jaeger S.U., Schroeder B.O., Meyer-Hoffert U., Courth L., Fehr S.N., Gersemann M., et al. Cell-mediated reduction of human β-defensin 1: a major role for mucosal thioredoxin. Mucosal Immunol 2013, [(Epub ahead of print) [Pubmed: 23571504]]. 10.1038/mi.2013.17.
45. Bucki R., Namiot D.B., Namiot Z., Savage P.B., Janmey P.A. Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13. J Antimicrob Chemother 2008, 62:329-335. [PubMed: 18456648].
46. McGuckin M.A., Lindén S.K., Sutton P., Florin T.H. Mucin dynamics and enteric pathogens. Nat Rev Microbiol 2011, 9:265-278. [PubMed: 21407243].
47. Wehkamp J., Stange E.F. Paneth's disease. J Crohns Colitis 2010, 4:523-531. [Pubmed: 21122555].
48. Peyrin-Biroulet L., Beisner J., Wang G., Nuding S., Oommen S.T., Kelly D., et al. Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci U S A 2010, 107:8772-8777. [PubMed: 20421464].
49. Wehkamp J., Salzman N.H., Porter E., Nuding S., Weichenthal M., Petras R.E., et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 2005, 102:18129-18134. [PubMed: 16330776].
50. Pullan R.D., Thomas G.A., Rhodes M., Newcombe R.G., Williams G.T., Allen A., et al. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut 1994, 35:353-359. [PubMed: 8150346].
51. Clamp J.R., Fraser G., Read A.E. Study of the carbohydrate content of mucus glycoproteins from normal and diseased colons. Clin Sci (Lond) 1981, 61:229-234. [PubMed: 7261546].
52. Raouf A.H., Tsai H.H., Parker N., Hoffman J., Walker R.J., Rhodes J.M. Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis. Clin Sci (Lond) 1992, 83:623-626. [PubMed: 1335401].
53. Braun A., Treede I., Gotthardt D., Tietje A., Zahn A., Ruhwald R., et al. Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis. Inflamm Bowel Dis 2009, 15:1705-1720. [PubMed: 19504612].