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Increase of Colonic Mast Cells in Obstructed Defecation and Their Relationship with Enteric Glia

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Abstract

Background

Mast cells are involved in visceral hypersensitivity and motor activity of the gastrointestinal tract. However, there is almost no information concerning mast cells in constipated patients.

Aims

The purpose of this study was to investigate mast cells distribution in all colonic layers in controls and severely constipated patients with obstructed defecation.

Methods

Full-thickness specimens from colons of patients undergoing surgery for obstructed defecation due to refractoriness to other therapeutic interventions (n = 11), compared to controls, were obtained and the number of mast cells (evaluated by specific monoclonal antibodies) were counted in the whole viscus and in the various colonic segments (cecum, ascending, transverse, descending, and sigmoid).

Results

Compared to controls, constipated patients had significantly higher numbers of mast cells, both as an overall number and in single colonic segments. This increase was especially evident in the mucosa and submucosa. Mast cells were homogeneously represented in the various segment of the large bowel, in both controls and patients. Degranulated mast cells were found to be close to enteric glial cells and glial filaments.

Conclusions

Colonic mast cells are increased in obstructed defecation patients. This might represent a vicariating mechanism to the impaired colonic propulsive activity of these patients.

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References

  1. Mikkelsen HB. Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions. J Cell Mol Med. 2010;14:818–832.

    Article  PubMed  CAS  Google Scholar 

  2. O’Sullivan M, Clayton N, Breslin NP, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000;12:449–457.

    Article  PubMed  Google Scholar 

  3. Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.

    Article  PubMed  Google Scholar 

  4. Park JH, Rhee PL, Kim HS, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:71–78.

    Article  PubMed  Google Scholar 

  5. Piche T, Saint-Paul MC, Dainese R, et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 2008;57:468–473.

    Article  PubMed  CAS  Google Scholar 

  6. Goral V, Kucukoner M, Buyukbayram H. Mast cells count and serum cytokine levels in patients with irritable bowel syndrome. Hepatogastroenterology. 2010;57:751–754.

    PubMed  Google Scholar 

  7. Barbara G, Wang B, Stanghellini V, et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132:26–37.

    Article  PubMed  CAS  Google Scholar 

  8. Pinheiro SW, Rua AM, Etchebehere RM, et al. Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon. Rev Soc Bras Med Trop. 2003;36:461–466.

    Article  PubMed  Google Scholar 

  9. da Silveira AB, Adad SJ, Correa-Oliveira R, Furness JB, D’Avila Reis D. Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon. Parasitology. 2007;134:789–796.

    Article  PubMed  CAS  Google Scholar 

  10. Iantorno G, Bassotti G, Kogan Z, et al. The enteric nervous system in chagasic and idiopathic megacolon. Am J Surg Pathol. 2007;31:460–468.

    Article  PubMed  Google Scholar 

  11. Kobayashi H, Yamataka A, Fujimoto T, Lane GJ, Miyano T. Mast cells and gut nerve development: implications for Hirschsprung’s disease and intestinal neuronal dysplasia. J Pediatr Surg. 1999;34:543–548.

    Article  PubMed  CAS  Google Scholar 

  12. Demirbilek S, Ozardali HI, Aydm G. Mast-cells distribution and colonic mucin composition in Hirschsprung’s disease and intestinal neuronal dysplasia. Pediatr Surg Int. 2001;17:136–139.

    Article  PubMed  CAS  Google Scholar 

  13. Hermanowicz A, Debek W, Dzienis-Koronkiewicz E, Chyczewski L. Topography and morphometry of intestinal mast cells in children with Hirschsprung’s disease. Folia Histochem Cytobiol. 2008;46:65–68.

    Article  PubMed  Google Scholar 

  14. Yadav AK, Mishra K, Mohta A, Agarwal S. Hirschsprung’s disease: is there a relationship between mast cells and nerve fibers? World J Gastroenterol. 2009;15:1493–1498.

    Article  PubMed  Google Scholar 

  15. Velio P, Bassotti G. Chronic idiopathic constipation: pathophysiology and treatment. J Clin Gastroenterol. 1996;22:190–196.

    Article  PubMed  CAS  Google Scholar 

  16. Khaikin M, Wexner SD. Treatment strategies in obstructed defecation and fecal incontinence. World J Gastroenterol. 2006;12:3168–3173.

    PubMed  Google Scholar 

  17. Bassotti G, Villanacci V, Nascimbeni R, et al. Colonic mast cells in controls and slow transit constipation patients. Aliment Pharmacol Ther. 2011;34:92–99.

    Article  PubMed  CAS  Google Scholar 

  18. Bassotti G, Villanacci V. Can “functional” constipation be considered as a form of enteric neuro-gliopathy? Glia. 2011;59:345–350.

    Article  PubMed  Google Scholar 

  19. Bassotti G, Villanacci V, Nascimbeni R, et al. Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation. Mod Pathol. 2007;20:367–374.

    Article  PubMed  Google Scholar 

  20. Thompson WG, Longstreth GF, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gut. 1999;45:43–47.

    Google Scholar 

  21. Bassotti G, Chistolini F, Sietchiping-Nzepa F, et al. Biofeedback for pelvic floor dysfunction in constipation. BMJ. 2004;328:393–396.

    Article  PubMed  CAS  Google Scholar 

  22. Bharucha AE, Wald A, Enck P, Rao S. Functional anorectal disorders. Gastroenterology. 2006;130:1510–1518.

    Article  PubMed  Google Scholar 

  23. de Lorijn F, Kremer LC, Reitsma JB, Benninga MA. Diagnostic tests in Hirschsprung disease: a systematic review. J Pediatr Gastroenterol Nutr. 2006;42:496–505.

    Article  PubMed  Google Scholar 

  24. Walls AF, Jones DB, Williams JH, Church MK, Holgate ST. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol. 1990;162:119–126.

    Article  PubMed  CAS  Google Scholar 

  25. Abonia JP, Blanchard C, Butz BB, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126:140–149.

    Article  PubMed  CAS  Google Scholar 

  26. Barbara G, Stanghellini V, De Giorgio R, Corinaldesi R. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil. 2006;18:6–17.

    Article  PubMed  CAS  Google Scholar 

  27. Dunlop SP, Jenkins D, Spiller RC. Age-related decline in rectal mucosal lymphocytes and mast cells. Eur J Gastroenterol Hepatol. 2004;16:1011–1015.

    Article  PubMed  Google Scholar 

  28. Li CY, Dry SM. Are c-kit and mast cell tryptase more effective at identifying mucosal mast cells in GI biopsies? Mod Pathol. 2004;17(suppl. 1):121A.

    Google Scholar 

  29. Walls AF, Jones DB, Williams JH, Church MK, Holgate ST. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol. 1990;162:119–126.

    Article  PubMed  CAS  Google Scholar 

  30. Minnei F, Wetzels C, De Hertogh G, et al. Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. Virchows Arch. 2006;448:262–268.

    Article  PubMed  Google Scholar 

  31. Siegert SI, Diebold J, Ludolph-Hauser D, Lohrs U. Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? Am J Clin Pathol. 2004;122:560–565.

    Article  PubMed  Google Scholar 

  32. Cremon C, Gargano L, Morselli-Labate AM, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104:392–400.

    Article  PubMed  CAS  Google Scholar 

  33. Ortiz-Lucas M, Saz-Peiró P, Sebastián-Domingo JJ. Irritable bowel syndrome immune hypothesis. Part one: the role of lymphocytes and mast cells. Rev Esp Enferm Dig. 2010;102:637–647.

    PubMed  CAS  Google Scholar 

  34. Ohman L, Simrén M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010;7:163–173.

    Article  PubMed  Google Scholar 

  35. Klooker TK, Braak B, Koopman KE, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010;59:1213–1221.

    Article  PubMed  CAS  Google Scholar 

  36. Frieling T, Meis K, Kolck UW, et al. Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome. Z Gastroenterol. 2011;49:191–194.

    Article  PubMed  CAS  Google Scholar 

  37. Feng BS, He SH, Zheng PY, Wu L, Yang PC. Mast cells play a crucial role in Staphylococcus aureus peptidoglycan-induced diarrhea. Am J Pathol. 2007;171:537–547.

    Article  PubMed  CAS  Google Scholar 

  38. Perrier C, Thierry AC, Mercenier A, Corthésy B. Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice. Clin Exp Allergy. 2010;40:153–162.

    Google Scholar 

  39. Jakate S, Demeo M, John R, Tobin M, Keshavarzian A. Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med. 2006;130:362–367.

    PubMed  Google Scholar 

  40. Söderholm JD. Mast cells and mastocytosis. Dig Dis. 2009;27:129–136.

    Google Scholar 

  41. Leon A, Buriani A, Dal Toso R, et al. Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA. 1994;91:3739–3743.

    Article  PubMed  CAS  Google Scholar 

  42. Nilsson G, Forsberg-Nilsson K, Xiang Z, et al. Human mast cells express functional TrkA and are a source of nerve growth factor. Eur J Immunol. 1997;27:2295–2301.

    Article  PubMed  CAS  Google Scholar 

  43. Bassotti G, Villanacci V, Maurer CA, et al. The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation. Gut. 2006;55:41–46.

    Article  PubMed  CAS  Google Scholar 

  44. Narducci F, Bassotti G, Gaburri M, Morelli A. Twenty four hour manometric recording of colonic motor activity in healthy man. Gut. 1987;28:17–25.

    Article  PubMed  CAS  Google Scholar 

  45. Bassotti G, Gaburri M. Manometric investigation of high-amplitude propagated contractile activity of the human colon. Am J Physiol. 1988;255:G660–G664.

    PubMed  CAS  Google Scholar 

  46. Bassotti G, Gaburri M, Imbimbo BP, et al. Colonic mass movements in idiopathic chronic constipation. Gut. 1988;29:1173–1179.

    Article  PubMed  CAS  Google Scholar 

  47. Bassotti G, Chiarioni G, Vantini I, et al. Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation. Dig Dis Sci. 1994;39:1558–1564.

    Article  PubMed  CAS  Google Scholar 

  48. Hervé S, Savoye G, Behbahani A, et al. Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation. Neurogastroenterol Motil. 2004;16:397–402.

    Article  PubMed  Google Scholar 

  49. Rao SS, Sadeghi P, Beaty J, Kavlock R. Ambulatory 24-hour colonic manometry in slow-transit constipation. Am J Gastroenterol. 2004;99:2405–2416.

    Article  PubMed  Google Scholar 

  50. Dinning PG, Zarate N, Hunt LM, et al. Pancolonic spatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation. Neurogastroenterol Motil. 2010;22:e340–e349.

    Article  PubMed  CAS  Google Scholar 

  51. Bassotti G, Clementi M, Antonelli E, Pelli MA, Tonini M. Low-amplitude propagated contractile waves: a relevant propulsive mechanism of human colon. Dig Liver Dis. 2001;33:36–40.

    Article  PubMed  CAS  Google Scholar 

  52. Bazzocchi G, Ellis J, Villanueva-Meyer J, et al. Effect of eating on colonic motility and transit in patients with functional diarrhea. Simultaneous scintigraphic and manometric evaluations. Gastroenterology. 1991;101:1298–1306.

    PubMed  CAS  Google Scholar 

  53. Bassotti G, de Roberto G, Chistolini F, et al. Twenty-four-hour manometric study of colonic propulsive activity in patients with diarrhea due to inflammatory (ulcerative colitis) and non-inflammatory (irritable bowel syndrome) conditions. Int J Colorectal Dis. 2004;19:493–497.

    Article  PubMed  Google Scholar 

  54. Bassotti G, Villanacci V, Mazzocchi A, et al. Colonic propulsive and postprandial motor activity in patients with ulcerative colitis in remission. Eur J Gastroenterol Hepatol. 2006;18:507–510.

    Article  PubMed  Google Scholar 

  55. Bassotti G, Chistolini F, Nzepa FS, Morelli A. Colonic propulsive impairment in intractable slow-transit constipation. Arch Surg. 2003;138:1302–1304.

    Article  PubMed  Google Scholar 

  56. Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology. 1989;97:575–585.

    PubMed  CAS  Google Scholar 

  57. Williams RM, Berthoud HR, Stead RH. Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa. Neuroimmunomodulation. 1997;4:266–270.

    PubMed  CAS  Google Scholar 

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Bassotti, G., Villanacci, V., Nascimbeni, R. et al. Increase of Colonic Mast Cells in Obstructed Defecation and Their Relationship with Enteric Glia. Dig Dis Sci 57, 65–71 (2012). https://doi.org/10.1007/s10620-011-1848-y

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  • DOI: https://doi.org/10.1007/s10620-011-1848-y

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