Pathogenesis of irritable bowel syndrome: The mast cell connection

Santos, Javier; Guilarte, Mar; Alonso, Carmen; Malagelada, Juan–R.

doi:10.1080/00365520410009410

Cited by 67 publications

(58 citation statements)

References 122 publications

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“…9 Most MCs in the gastrointestinal mucosa are MC T (containing only tryptase), whereas the dominating phenotype in submucosa is MC TC (containing both tryptase and chymase). 11 Generally, MCs can be activated by an IgE dependent way via the high-affinity receptor FcεRI which play a key role in allergic reactions. Besides this classical and most effective way, IgG, IgA, Igfree-light chains (IgFLC) and even complements (C3a and C5a) might also play a role via binding to the related receptors expressed on MCs.…”

Section: Mast Cells In the Human Gutmentioning

confidence: 99%

“…4 Moreover, amounts of immune-independent stimulus could trigger MCs activation, such as neuro-hormonal stimuli including neurotransmitters, neuropeptides, hormones and growth factors, particularly substance P (SP) or calcitonin gene-related peptide (CGRP) released from nociceptive endings and corticotropin releasing factor (CRF) induced by psychological stress, which are important in the regulation of gut functions. 9,11,12 Other biological factors such as bacteria components (via Toll-like receptors or other pattern recognition receptors), and some physiochemical factors also could lead to MCs activation. 11,13 Upon activation, MCs release bioactive substances preformed in granules (histamine, enzymes, and heparin) and newly synthesized cytokine, chemokines, and lipid metabolites (Table 1).…”

Section: Mast Cells In the Human Gutmentioning

confidence: 99%

“…9,11,12 Other biological factors such as bacteria components (via Toll-like receptors or other pattern recognition receptors), and some physiochemical factors also could lead to MCs activation. 11,13 Upon activation, MCs release bioactive substances preformed in granules (histamine, enzymes, and heparin) and newly synthesized cytokine, chemokines, and lipid metabolites (Table 1). 4,9,10,14 These mediators contribute to the broad spectrum of regulating effects of MCs in the gut, and participate in multiple pathophysiological processes and diseases beyond allergy, which including IBS, functional dyspepsia, inflam- (CCL4), CCL5, CCL7, CCL8, CCL11, CCL13, CCL16, CCL17, CCL20, CCL22, CXCL1, CXCL2, CXCL3, CXCL10, MIF, LIF Growth factors VEGF, TGF-β, basic FGF, NGF, NT-3, GM-CSF, M-CSF, SCF, EGF, PDGF Eicosanoids Leukotrienes (LTB4, LTC4, LTD4, LTE4) Prostaglandins (PGD2, PGE2), PAF Other mediators Nitric oxide, SP, VIP, ATP, CRF, Urocortin TNF-α, tumor necrosis factor-α; IL, interleukins; VEGF, vascular endothelial growth factor; INF-γ, interferon-γ; CCL, chemokine (C-C motif) ligand; MCP, monocyte chemoattractant protein; MIP, macrophage inflammation protein; CXCL, chemokine (C-X-C motif) ligand; MIF, macrophage migration inhibitory factor; LIF, leukemia inhibitor factor; TGF-β, transforming growth factor-β; FGF, fibroblast growth factor; NGF, nerve growth factor; NT-3, neurotrophin-3; GM-CSF, granulocyte-macrophage colony stimulating factor; M-CSF, macrophage colony-stimulating factor; SCF, stem cell factor; EGF, epidermal growth factor; PDGF, platelet derived growth factor; LT, leukotrienes; PG, prostaglandins; PAF, platelet-activating factor; SP, substance P; VIP, vasoactive intestinal peptide; ATP, adenosine triphosphate; CRF, corticotropin releasing factor.…”

Section: Mast Cells In the Human Gutmentioning

confidence: 99%

“…11,13 The density of MCs in both the small and large bowel may be increased in patients with IBS, but the results are somewhat inconsistent. Some studies demonstrated the number of MCs or the area of mucosa occupied by MCs was increased in IBS patients, 5 moreover, it varies in different genders, 15 in distinct bowel segments 16 and in subgroups of IBS with higher MCs counts in diarrhea-predominant IBS (D-IBS) patients than constipationpredominant IBS (C-IBS) patients.…”

Section: Mast Cells and Irritable Bowel Syndrome: The Presentmentioning

confidence: 99%

“…14 Plenty of evidence has confirmed that endings of postganglionic sympathetic, peptidergic and vagal fibers, and enteric neurons are in close proximity to MCs. 10,11 An estimated 70% of intestinal mucosal MCs are in direct contact with nerves, and another 20% are within 2 μm. 10 Furthermore, neuro-anatomical studies have provided strong evidence for the direct innervation of MCs, including the intrinsic and extrinsic nerves, particularly, the nonadrenergic noncholinergic nerves.…”

Section: Mast Cells Activation and Gastrointestinal Functions In Irrimentioning

confidence: 99%

See 4 more Smart Citations

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Section: Mast Cells In the Human Gutmentioning

confidence: 99%