Role of Neuropeptides in Gastrointestinal Manifestations of Systemic Mastocytosis and Similarities with Irritable Bowel Syndrome
DOI:
https://doi.org/10.24950/rspmi.2022.01.301Keywords:
Diarrhea, Gastrointestinal Tract, Irritable Bowel Syndrome, Mast Cells, Mastocytosis, Systemic, Neuropeptides, Substance P, Vasoactive Intestinal PeptideAbstract
Systemic mastocytosis (SM) is a rare myeloproliferative neoplasm characterized by the extracutaneous proliferation of clonal MC in the bone marrow or other extramedullary sites with or without cutaneous involvement. GastrointestinaI (GI) manifestations, consisting of abdominal pain, diarrhea and malabsorption with various degrees of severity, are frequent in patients with SM and can result from mediator release or direct MC infiltration of the GI tract. Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic and recurrent abdominal pain or discomfort associated with defecation or change in bowel habit. The interaction between immune system and neuropeptides and the enhancement of an inflammatory mucosal response with an increase in immune cells is a key feature of IBS. Previous evidence shows that there is an increased number of MC in the intestinal and colonic mucosa of IBS patients. MC are present in the GI and their activation has been associated to some pro-secretory neurotransmitters such as substance P and vasoactive intestinal peptide in the proximity of enteric nerves suggesting a bidirectional regulatory pathway with neurocrine control of MC activation. Research concerning the role of enteric MC in both SM and IBS is still scarce as well as their link to neuropeptides. Likewise, more evidence is needed regarding MC and neuropeptides interaction in order to further comprehend the pathophysiology of the GI manifestations of SM and IBS, and the boundaries between these pathologies. In this review we hypothesize that GI symptoms SM and in IBS have similar mechanisms and mediators, with a special focus in the role of mucosal MC and neuropeptides.
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References
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 27:2391-405. doi: 10.1182/ blood-2016-03-643544.
Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129:1420-7. doi: 10.1182/blood-2016-09-731893.
Zanelli M, Pizzi M, Sanguedolce F, Zizzo M, Palicelli A, Soriano A, et al. Gastrointestinal Manifestations in Systemic Mastocytosis: The Need of a Multidisciplinary Approach. Cancers. 2021;13:3316.
Sébastian Domingo JJ. Irritable bowel syndrome. Med Clin. 2021;158:76- 81. doi: 10.1016/j.medcli.2021.04.029.
Moon TC, Dean Befus A, Kulka M. Mast cell mediators: Their differential release and the secretory pathways involved. Front Immunol. 2014;5:1–18.
Traina G. The role of mast cells in the gut and brain. J Integr Neurosci. 2021;20:185-96. doi: 10.31083/j.jin.2021.01.313.
Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579–623.
Cherner JAYA, Jensen RT, Dubois A, Dorisio TMO, Gardner JD, Metcalfe DD. Gastrointestinal Dysfunction in Systemic Mastocytosis: A Prospective Study. Gastroenterology. 1988;95:657–67.
Doyle L, Sepehr G, Hamilton M, Akin C, Castells M. A clinicopathological study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessement of the mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol. 2014;38:832–43.
Kirsch R, Geboes K, Shepherd NA, de Hertogh G, Di Nicola N, Lebel S, et al. Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. Mod Pathol. 2008;21:1508–16.
Lee JK, Whittaker SJ, Enns RA, Zetler P. Gastrointestinal manifestations of systemic mastocytosis. World J Gastroenterol. 2008;14:7005–8.
Ferguson J, Thompson RP, Greaves MW. Intestinal mucosal mast cells: enumeration in urticaria pigmentosa and systemic mastocytosis. Br J Dermatol. 1988;119:573–8.
Siegert SI, Diebold J, Ludolph-Hauser D, Löhrs U. Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? Am J Clin Pathol. 2004;122:560–5.
Miner PBJ. The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. J Invest Dermatol. 1991;96:40S-43S; discussion 43S-44S, 60S-65S.
Doyle LA, Hornick JL. Pathology of extramedullary mastocytosis. Immunol Allergy Clin North Am. 2014;34:323–39.
Scolapio JS, Wolfe J 3rd, Malavet P, Woodward TA. Endoscopic findings in systemic mastocytosis. Gastrointest Endosc. 1996;44:608–10.
Hahn HP, Hornick JL. Immunoreactivity for CD25 in gastrointestinalmucosal mast cells is specific for systemic mastocytosis. Am J Surg Pathol. 2007;31:1669–76.
Shih AR, Deshpande V, Ferry JA, Zukerberg L. Clinicopathological characteristics of systemic mastocytosis in the intestine. Histopathology. 2016;69:1021–7.
Vajpeyi R. Gastrointestinal manifestations of systemic mastocytosis. Diagnostic Histopathol. 2016;22:167–9.
Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J. Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gas troenterology. 1989;97:575–85.
Marney SRJ. Mast cell disease. Allergy Proc. 1992;13303–10.
Ramsay DB, Stephen S, Borum M, Vltaggio L. Mast cells in gastrointestinal disease. Gastroenterol Hepatol. 2010;6:772–7.
Sokol H, Georgin-lavialle S, Canioni D, Chandesris M, Suarez F, Launay J, et al. Gastrointestinal manifestations in mastocytosis : A study of 83 patients. J Allergy Clin Immunol. 2013;132:866–73.
Libel R, Biddle WL, Miner PBJ. Evaluation of anorectal physiology in patients with increased mast cells. Dig Dis Sci. 1993;38:877–81.
Tzankov A, Duncavage E, Craig FE, Kelemen K, King RL, Orazi A, et al. Mastocytosis: Lessons Learned From the 2019 Society for Hematopathology/European Association for Haematopathology Workshop. Am J Clin Pathol. 2021;155:239–66. doi:10.1093/ajcp/aqaa183
Behdad A, Owens S. Systemic mastocytosis involving the gastrointestinal tract: case report and review. Arch Pathol Lab Med. 2013;137:1220–3.
Bedeir A, Jukic DM, Wang L, Mullady DK, Regueiro M, Krasinskas AM. Systemic mastocytosis mimicking inflammatory bowel disease: A case report and discussion of gastrointestinal pathology in systemic mastocytosis. Am J Surg Pathol. 2006;30:1478–82.
Zanelli M, Pai RK, Zorzi MG, Zizzo M, Martino G, Morelli L, et al. Gastroin testinal Mastocytosis: A Potential Diagnostic Pitfall to Be Aware. Int J Surg Pathol. 2019;27:643-6. doi: 10.1177/1066896919846648.
Johncilla M, Jessurun J, Brown I, Hornick JL, Bellizzi AM, Shia J, et al. Are Enterocolic Mucosal Mast Cell Aggregates Clinically Relevant in Patients Without Suspected or Established Systemic Mastocytosis? Am J Surg Pathol. 2018;42:1390–5.
Tharp MD. The Spectrum of Mastocytosis. Am J Med Sci. 1985;289:119- 132.
Wood JD. Enteric neuroimmunophysiology and pathophysiology. Gastroenterology. 2004; 127:635-657.
Santos J, Yates D, Guilarte M, Vicario M, Alonso C, Perdue MH. Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon. Psychoneuroendocrinology. 2008;33:1248-56.
Keita Å V., Söderholm JD, Ericson AC. Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells. Neurogastroenterol Motil. 2010;22:e221-2.
Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77:1033- 79.
Yu LCH, Perdue MH. Role of mast cells in intestinal mucosal function: Studies in models of hypersensitivity and stress. Immunol Rev. 2001;179:61- 73.
Hon WK, Pothoulakis C. Immunomodulatory properties of substance P: The gastrointestinal system as a model. In: Annals of the New York Academy of Sciences. 2006;1088:23-40.
Raithel M, Schneider HT, Hahn EG. Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease. Scand J Gastroenterol. 1999;34:496-503.
Wang L, Stanisz AM, Wershil BK, Galli SJ, Perdue MH. Substance P induces ion secretion in mouse small intestine through effects on enteric nerves and mast cells. Am J Physiol - Gastrointest Liver Physiol. 1995;269:G85-92.
Janiszewski J, Bienenstock J, Blennerhassett MG. Picomolar doses of substance P trigger electrical responses in mast cells without degranulation. Am J Physiol - Cell Physiol. 1994;267:C138-45.
van Diest SA, Stanisor OI, Boeckxstaens GE, de Jonge WJ, van den Wijngaard RM. Relevance of mast cell-nerve interactions in intestinal nociception. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2012;1822:74-84.
Larsson LI, Fahrenkrug J, Schaffalitzky De Muckadell O, Sundler F, Håkanson R, Rehfeld JR. Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons. Proc Natl Acad Sci U S A. 1976;73:3197- 200
Casado-Bedmar M, Heil SDS, Myrelid P, Söderholm JD, Keita Å V. Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis. Neurogastroenterol Motil. 2019;31:e13503.
Jayawardena D, Guzman G, Gill RK, Alrefai WA, Onyuksel H, Dudeja PK. Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine. Am J Physiol - Gastrointest Liver Physiol. 2017;313:G16-G25.
EKLUND S, JODAL M, LUNDGREN O, SJOQVIST A. Effects of vasoactive intestinal polypeptide on blood flow, motility and fluid transport in the gastrointestinal tract of the cat. Acta Physiol Scand. 1979;105:461-8.
Fahrenkrug J. Transmitter Role of Vasoactive Intestinal Peptide. Pharmacol Toxicol. 1993;72:354-63.
Iwasaki M, Akiba Y, Kaunitz JD. Recent advances in vasoactive intestinal peptide physiology and pathophysiology: Focus on the gastrointestinal system. F1000Research. 2019;8:1–13.
Palsson OS, Morteau O, Bozymski EM, Woosley JT, Sartor RB, Davies MJ, et al. Elevated vasoactive intestinal peptide concentrations in patients with irritable bowel syndrome. Dig Dis Sci. 2004;49:1236-43.
Zhang H, Yan Y, Shi R, Lin Z, Wang M, Lin L. Correlation of gut hormones with irritable bowel syndrome. Digestion. 2008;78:72-6.
Duffy LC, Zielezny MA, Riepenhoff-Talty M, Byers TE, Marshall J, Weiser MM, et al. Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease. Dig Dis Sci. 1989;34:1528- 35.
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional Bowel Disorders. Gastroenterology. 2006;130:1480-91.
Drossman DA, Creed FH, Olden KW, Svedlund J, Toner BB, Whitehead WE. Psychosocial aspects of the functional gastrointestinal disorders. Gut. 1999;45 Suppl 2:II25-30.
Uranga JA, Martínez V, Abalo R. Mast cell regulation and irritable bowel syndrome: Effects of food components with potential nutraceutical use. Molecules. 2020;25:4314.
Santos J, Guilarte M, Alonso C, Malagelada JR. Pathogenesis of irritable bowel syndrome: the mast cell connection. Scand J Gastroenterol. 2005;40:129–40.
Barbara G, Stanghellini V, De Giorgio R, Corinaldesi R. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroen terol Motil. 2006;18:6–17.
Gurish MF, Austen KF. The diverse roles of mast cells. Journal of Experimental Medicine. 2001;194:f1-f6.
Guilarte M, Santos J, De Torres I, Alonso C, Vicario M, Ramos L, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56:203–9.
Park JH, RHEE P, Kim HS, Lee JH, KIM Y, Kim JJ, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:71–8.
Walker MM, Talley NJ, Prabhakar M, Pennaneac’h CJ, Aro P, Ronkainen J, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–73.
Piche T, Saint-Paul MC, Dainese R, Marine-Barjoan E, Iannelli A, Montoya ML, et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 2008;57:468-73.
Katinios G, Casado-Bedmar M, Walter SA, Vicario M, González-Castro AM, Bednarska O, et al. Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared with Irritable Bowel Syndrome and Health. Inflamm Bowel Dis. 2020;26:974-984.
Weston AP, Biddle WL, Bhatia PS, Miner PB. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993;38:1590-5.
O’sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000;12:449–58.
Park CH, Joo YE, Choi SK, Rew JS, Kim SJ, Lee MC. Activated Mast Cells Infiltrate in Close Proximity to Enteric Nerves in Diarrhea-predominant Irritable Bowel Syndrome. J Korean Med Sci. 2003;18:204-10.
Pang X, Boucher W, Triadafilopoulos G, Sant GR, Theoharides TC. Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Urology. 1996;47:436–8.
Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.
Bednarska O, Walter SA, Casado-Bedmar M, Ström M, Salvo-Romero E, Vicario M, et al. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syn drome. Gastroenterology. 2017;153:948-960.
Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, et al. Mast cell number, substance P and vasoactive intestinal peptide in irritable bowel syndrome with diarrhea. Scand J Gastroenterol. 2014;49:43–51.
Casado-Bedmar M, Keita Å V. Potential neuro-immune therapeutic targets in irritable bowel syndrome. Therapeutic Advances in Gastroenterology. 2020;13:1-15.
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