Nerve fiber overgrowth in patients with symptomatic diverticular disease.
diverticular disease
nerve fiber sprouting
neuroimmune interactions
symptomatic uncomplicated diverticular disease
Journal
Neurogastroenterology and motility
ISSN: 1365-2982
Titre abrégé: Neurogastroenterol Motil
Pays: England
ID NLM: 9432572
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
14
11
2018
revised:
10
01
2019
accepted:
01
02
2019
pubmed:
7
3
2019
medline:
25
8
2020
entrez:
7
3
2019
Statut:
ppublish
Résumé
Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.
Sections du résumé
BACKGROUND
Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula.
METHODS
Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers).
KEY RESULTS
No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells.
CONCLUSIONS AND INFERENCES
Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13575Informations de copyright
© 2019 John Wiley & Sons Ltd.
Références
Stollman N, Raskin JB. Diverticular disease of the colon. Lancet. 2004;363(9409):631-639.
Spiller RC. Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota. Neurogastroenterol Motil. 2015;27(3):305-312.
Cuomo R, Barbara G, Pace F, et al. Italian consensus conference for colonic diverticulosis and diverticular disease. United European Gastroenterol J. 2014;2(5):413-442.
Simpson J, Scholefield JH, Spiller RC. Origin of symptoms in diverticular disease. Br J Surg. 2003;90(8):899-908.
Clemens CH, Samsom M, Roelofs J, van Berge Henegouwen GP, Smout AJ. Colorectal visceral perception in diverticular disease. Gut. 2004;53(5):717-722.
Humes DJ, Simpson J, Smith J, et al. Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation. Neurogastroenterol Motil. 2012;24(4):318-e163.
Barbara G, Scaioli E, Barbaro MR, et al. Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease. Gut. 2017;66(7):1252-1261.
Barbara G, Cremon C, De Giorgio R, et al. Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome. Curr Gastroenterol Rep. 2011;13(4):308-315.
Cohen E, Fuller G, Bolus R, et al. Increased risk for irritable bowel syndrome after acute diverticulitis. Clin Gastroenterol Hepatol. 2013;11(12):1614-1619.
Cianci R, Frosali S, Pagliari D, et al. Uncomplicated diverticular disease: innate and adaptive immunity in human gut mucosa before and after rifaximin. J Immunol Res. 2014;2014:696812.
Dothel G, Barbaro MR, Boudin H, et al. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2015;148(5):1002-1011.e1004
Demir IE, Schafer KH, Tieftrunk E, Friess H, Ceyhan GO. Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity. Acta Neuropathol. 2013;125(4):491-509.
Barbara G, Feinle-Bisset C, Ghoshal UC, et al. The intestinal microenvironment and functional gastrointestinal disorders. Gastroenterology. 2016;150(6):1305-1318.
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(3):693-702.
Barbara G, Wang B, Stanghellini V, et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132(1):26-37.
Cremon C, Carini G, Wang B, et al. Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. Am J Gastroenterol. 2011;106(7):1290-1298.
Peery AF, Keku TO, Addamo C, et al. Colonic diverticula are not associated with mucosal inflammation or chronic gastrointestinal symptoms. Clin Gastroenterol Hepatol. 2018;16(6):884-891.e881.
Horgan AF, McConnell EJ, Wolff BG, The S, Paterson C. Atypical diverticular disease: surgical results. Dis Colon Rectum. 2001;44(9):1315-1318.
Muller PA, Koscso B, Rajani GM, et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell. 2014;158(2):300-313.
Gabanyi I, Muller PA, Feighery L, Oliveira TY, Costa-Pinto FA, Mucida D. Neuro-immune interactions drive tissue programming in intestinal macrophages. Cell. 2016;164(3):378-391.
De Schepper S, Verheijden S, Aguilera-Lizarraga J, et al. Self-maintaining gut macrophages are essential for intestinal homeostasis. Cell. 2018;175(2):400-415.
Bassotti G, Battaglia E, Bellone G, et al. Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease. J Clin Pathol. 2005;58(9):973-977.
Golder M, Burleigh DE, Belai A, et al. Smooth muscle cholinergic denervation hypersensitivity in diverticular disease. Lancet. 2003;361(9373):1945-1951.
Iwase H, Sadahiro S, Mukoyama S, Makuuchi H, Yasuda M. Morphology of myenteric plexuses in the human large intestine: comparison between large intestines with and without colonic diverticula. J Clin Gastroenterol. 2005;39(8):674-678.
Spiller R. How inflammation changes neuromuscular function and its relevance to symptoms in diverticular disease. J Clin Gastroenterol. 2006;40(Suppl 3):S117-S120.
Stoss F, Meier-Ruge W. Experience with neuronal intestinal dysplasia (NID) in adults. Eur J Pediatr Surg. 1994;4(5):298-302.
Deduchovas O, Saladzinskas Z, Tamelis A, Pavalkis D, Pauziene N, Pauza DH. Morphologic pattern of myenteric neural plexus in colonic diverticular disease. A whole-mount study employing histochemical staining for acetylcholinesterase. Ann Anat. 2008;190(6):525-530.
Simpson J, Sundler F, Humes DJ, Jenkins D, Scholefield JH, Spiller RC. Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. Neurogastroenterol Motil. 2009;21(8):847-e858.
Benowitz LI, Routtenberg A. GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 1997;20(2):84-91.
Byers MR, Taylor PE, Khayat BG, Kimberly CL. Effects of injury and inflammation on pulpal and periapical nerves. J Endod. 1990;16(2):78-84.
Lourenssen S, Wells RW, Blennerhassett MG. Differential responses of intrinsic and extrinsic innervation of smooth muscle cells in rat colitis. Exp Neurol. 2005;195(2):497-507.
Lang BT, Wang J, Filous AR, Au NP, Ma CH, Shen Y. Pleiotropic molecules in axon regeneration and neuroinflammation. Exp Neurol. 2014;258:17-23.
Martini R, Willison H. Neuroinflammation in the peripheral nerve: cause, modulator, or bystander in peripheral neuropathies? Glia. 2016;64(4):475-486.
Liu XG, Pang RP, Zhou LJ, Wei XH, Zang Y. Neuropathic pain: sensory nerve injury or motor nerve injury? Adv Exp Med Biol. 2016;904:59-75.
Wohleb ES, Delpech JC. Dynamic cross-talk between microglia and peripheral monocytes underlies stress-induced neuroinflammation and behavioral consequences. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79(Pt A):40-48.
Tonchev AB, Boneva NB, Kaplamadzhiev DB, et al. Expression of neurotrophin receptors by proliferating glia in postischemic hippocampal CA1 sector of adult monkeys. J Neuroimmunol. 2008;205(1-2):20-24.
Samah B, Porcheray F, Gras G. Neurotrophins modulate monocyte chemotaxis without affecting macrophage function. Clin Exp Immunol. 2008;151(3):476-486.
Plunkett RJ, Ip NY, Asada H, et al. Trauma-induced striatal CNTF and BDNF mRNA in hemiparkinsonian rats. NeuroReport. 1997;8(2):507-511.
Hong JH, Park HM, Byun KH, Lee BH, Kang WC, Jeong GB. BDNF expression of macrophages and angiogenesis after myocardial infarction. Int J Cardiol. 2014;176(3):1405-1408.
Cavel O, Shomron O, Shabtay A, et al. Endoneurial macrophages induce perineural invasion of pancreatic cancer cells by secretion of GDNF and activation of RET tyrosine kinase receptor. Cancer Res. 2012;72(22):5733-5743.
Gu Y, Wang X, Wu G, et al. Artemisinin suppresses sympathetic hyperinnervation following myocardial infarction via anti-inflammatory effects. J Mol Histol. 2012;43(6):737-743.
Caroleo MC, Costa N, Bracci-Laudiero L, Aloe L. Human monocyte/macrophages activate by exposure to LPS overexpress NGF and NGF receptors. J Neuroimmunol. 2001;113(2):193-201.
Takano S, Uchida K, Inoue G, et al. Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. Clin Exp Immunol. 2017;190(2):235-243.
Batchelor PE, Porritt MJ, Nilsson SK, Bertoncello I, Donnan GA, Howells DW. Periwound dopaminergic sprouting is dependent on numbers of wound macrophages. Eur J Neurosci. 2002;15(5):826-832.
Batchelor PE, Porritt MJ, Martinello P, et al. Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge. Mol Cell Neurosci. 2002;21(3):436-453.
Wernli G, Hasan W, Bhattacherjee A, van Rooijen N, Smith PG. Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction. Basic Res Cardiol. 2009;104(6):681-693.
Wolf Y, Boura-Halfon S, Cortese N, et al. Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure. Nat Immunol. 2017;18(6):665-674.
Jin X. Gereau RWt. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci. 2006;26(1):246-255.
Greaves E, Temp J, Esnal-Zufiurre A, Mechsner S, Horne AW, Saunders PT. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. Am J Pathol. 2015;185(8):2286-2297.