The association of mast cells and serotonin in children with chronic abdominal pain of unknown etiology (original) (raw)
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World journal of gastrointestinal pathophysiology, 2012
To investigate interleukin-6 (IL-6), mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P in the gastrointestinal mucosa of children with abdominal pain. Formalin-fixed paraffin-embedded gastrointestinal biopsy blocks from patients (n = 48) with non-inflammatory bowel disease (irritable bowel syndrome and functional abdominal pain) and inflammatory bowel disease were sectioned and stained for IL-6, mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P. All children had chronic abdominal pain as part of their presenting symptoms. Biopsy phenotype was confirmed by a pathologist, blinded to patient information. Descriptive statistics, chi-square, and independent sample t tests were used to compare differences between the inflammatory and non-inflammatory groups. The cohort (n = 48), mean age 11.9 years (SD = 2.9), 54.2% females, 90% Caucasian, was comprised of a non-inflammatory (n = 26) and an inflammatory (n = 22) phenotype. There was a signific...
Diagnostic Pathology, 2009
Background: Mast cells reside within the connective tissue of a variety of tissues and all vascularized organs. Since 1996, few studies have been performed on mast cell density in gastrointestinal biopsies, mainly in adult age group. We recently studied mast cell density in pediatric age group on rather larger number of cases in a referral children hospital. Mast cell density was 12.6 ± 0.87 in 0.25 mm 2 (range: 0-81) in our study. Since we frequently encounter cases with rather normal gastric biopsies with no H.pylori, which mainly complain of chronic abdominal pain, we gathered those cases with mast cell density more than 30/0.25 mm 2. from 895 gastric biopsies and wanted to study their clinical and endoscopic findings and propose a new entity. Methods: Between April 2005 and May 2008, 895 children (< 14 years old), with gastrointestinal complaints who underwent endoscopy were selected and antral biopsies were obtained for histological examination. Among these children, those who had normal or erythematous (but not nodular or ulcerative) gastric mucosa on endoscopic view, plus pathologic report of normal mucosa or mild gastritis in addition to mast cell count more than 30/25 mm 2 , were chosen and a questionnaire was filled for each patient including clinical, endoscopic and pathologic findings. The statistical analysis was performed using SPSS, version 13 (SPSS Inc., Chicago, IL, USA). Results: Over a 3 year period of study, of 895 selected children, 86 patients fulfilled the entrance criteria. The major complaint of patients was recurrent abdominal pain. The mean mast cell density was 45.59 ± 13.81 in 0.25 mm 2 (range: 30-93). Among our cases, about 67.4% (n = 58) had 30 to 49, 23.3% (n = 20) had 50 to 69, 8.1% (n = 7) had 70 to 89 and 1.2% (n = 1) had 93 mast cells/0.25 mm 2 in their specimens Discussion: In 29% of our cases, neither endoscopic nor pathologic change was detected and only increase in mast cell number was reported and in others endoscopic and histopathological findings were negligible except increase in mast cells. In updated Sydney system (classification and grading of gastritis), no term is introduced which is in concordance with this group but we think that increased density of mast cells in these cases should not be overlooked and it may contribute to clinical manifestations in some way. We hope that further studies will direct us to institute therapeutic measurements in this regard.
Increased mast cells in the irritable bowel syndrome
Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven in¯ammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quanti®ed by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0±4) in haematoxylin and eosin stained sections. Mast cell volume density was signi®cantly (P < 0.05) higher in IBS (0.91 0.18; CI 0.79; 1.0) than normal controls (0.55 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular in®ltrate in the IBS group. MC were signi®cantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent in¯ammatory response, may be fundamental to the pathogenesis of IBS.
Mast cell–nerve axis with a focus on the human gut
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2012
This paper summarizes the current knowledge on the interactions between intestinal mast cells, enteric neurons and visceral afferents which are part of the gut brain axis. The focus of this review is on the relevance of the mast cell-nerve axis in the human intestine. Similarities and important differences in the organization of the mast cell-nerve axis between human and rodents are discussed. Functionally important human mast cell mediators with neural actions in the human ENS are histamine (H1-4 receptors), proteases (PAR1 receptors), several cytokines and chemokines and probably also serotonin (5-HT 3 receptors). On the other hand, mediator release from human intestinal mast cells is modulated by neuropeptides released from enteric and visceral afferent nerves. This article is part of a Special Issue entitled: Mast Cells in Inflammation.
Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome
Gastroenterology, 2007
Intestinal mast cell infiltration may participate to abdominal pain in irritable bowel syndrome (IBS) patients. However, the underlying mechanisms remain unknown. We assessed the effect of mast cell mediators released from the colonic mucosa of IBS patients on the activation of rat sensory neurons in vitro. Methods: Colonic mast cell infiltration and mediator release were assessed with quantitative immunoflorescence and immunoenzymatic assays. The effect of mucosal mediators was tested on mesenteric sensory nerve firing and Ca 2؉ mobilization in dorsal root ganglia in rats. Results: Mediators from IBS patients, but not controls, markedly enhanced the firing of mesenteric nerves (14.7 ؎ 3.2 imp/sec vs 2.8 ؎ 1.5 imp/sec; P < .05) and stimulated mobilization of Ca 2؉ in dorsal root ganglia neurons (29% ؎ 4% vs 11% ؎ 4%; P < .05). On average, 64% of dorsal root ganglia responsive to mediators were capsaicin-sensitive, known to mediate nociception. Histamine and tryptase were mainly localized to mucosal mast cells. IBS-dependent nerve firing and Ca 2؉ mobilization were correlated with the area of the colonic lamina propria occupied by mast cells (r ؍ 0.74; P < .01, and r ؍ 0.78; P < .01, respectively). IBS-dependent excitation of dorsal root ganglia was inhibited by histamine H 1 receptor blockade and serine protease inactivation (inhibition of 51.7%; P < .05 and 74.5%; P < .05; respectively). Conclusions: Mucosal mast cell mediators from IBS patients excite rat nociceptive visceral sensory nerves. These results provide new insights into the mechanism underlying visceral hypersensitivity in IBS.
American Journal of Gastroenterology, 2011
Serotonin (5-hydroxytryptamine, 5-HT) metabolism may be altered in gut disorders, including in the irritable bowel syndrome (IBS). We assessed in patients with IBS vs. healthy controls (HCs) the number of colonic 5-HT-positive cells; the amount of mucosal 5-HT release; their correlation with mast cell counts and mediator release, as well as IBS symptoms; and the effects of mucosal 5-HT on electrophysiological responses in vitro .
Irritable bowel syndrome - An inflammatory disease involving mast cells
Asia Pacific Allergy, 2011
Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder -that is the presence of symptoms in the absence of demonstrable pathological abnormalities. In recent times, low grade inflammatory infiltrates in both the small and large bowel of some patients with IBS -often rich in mast cells, along with serological markers of low grade inflammation have focussed attention on IBS as an inflammatory disease. The observation that mast cells often lie in close association to enteric neurons, and in-vitro and in-vivo animal studies demonstrating that mast cell mediators may influence enteric motility provides a biologically plausible causal mechanism in IBS. Pilot studies on patients with IBS using the mast cell stabiliser sodium cromoglycate ('proof of concept') have been encouraging. The essential question remains why mast cells infiltrate the bowel of IBS patients. A disturbance of the 'braingut axis' is the current favoured hypothesis, whereby childhood stress or psychiatric comorbidity act via neuro-immune mechanisms to modulate low grade inflammation. An alternative hypothesis is that food allergy may be responsible. Serum specific IgE, and skin prick tests are not elevated in IBS patients, suggesting type 1 IgE mediated food allergy is not the cause. However questionnaire based studies indicate IBS patients have higher rates of atopic disease, and increased bronchial reactivity to methacholine has been demonstrated. In this review, we highlight the potential role of mast cells in IBS, and current and future research directions into this intriguing condition.
Quantitative Evaluation of Mucosal Mast Cells in the Colon in Patients with Irritable Bowel Syndrome
TAJ: Journal of Teachers Association, 2022
Background: Recent studies have shown that mast cells play an important role in the pathogenesis of irritable bowel syndrome as they release variable mediators which alter enteric nerve and smooth muscle function. The aim of this study was to determine whether mucosal mast cells were increased in the colonic mucosa of IBS patients compared to controls. Materials and Methods: This case-control study was conducted in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during the period from April 2016 to March 2017 on cases of IBS and comparison group. We recruited 25 IBS patients and 25 healthy controls for this study. Colonoscopic biopsy was taken from the caecum, ascending colon, descending colon, and rectum. Tissue was stained with Giemsa, and then quantitative evaluation of mast cells was performed. Mast cells counts were compared between the two groups of patients. Results: Mast cells were significantly higher in the caecum, ascending colon, d...