Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastro-intestinal tract is highly innervated by both intrinsic and extrinsic sensory nerves and this neuronal component is thought to play a role in local inflammatory responses. This in vivo study was designed to determine the function of substance P and the tachykinin NK1 receptor in the pathogenesis of inflammatory bowel disease by the use of the specific antagonist RP 67580. The dinitrofluorobenzene (DNFB)-induced colonic hypersensitivity model is associated with increased levels of substance P in the colon. The tachykinin NK1 receptor antagonist RP 67580 was used to investigate the role of substance P on the development of diarrhea, mast cell infiltration and activation, colonic tissue damage, hypertrophy of colonic lymphoid structures and leukocyte infiltration. The formation of watery diarrhea could completely be abrogated by treatment with RP 67580 in DNFB-sensitized animals 72 h after challenge. Antagonizing the tachykinin NK1 receptor in these animals also resulted in significantly reduced colonic patch hypertrophy, leukocyte recruitment and tissue damage. Total levels of substance P in the colon of DNFB-sensitized mice treated with the inactive enantiomer of the tachykinin NK1 receptor antagonist were significantly higher compared to DNFB-sensitized mice treated with RP 67580 72 h after challenge. Although RP 67580 was capable of reducing the total number of mast cells present in the colon, mast cell activation was not affected by this treatment. In conclusion, in this chemically-induced immunological model for inflammatory bowel disease we demonstrated an important role for tachykinin NK1 receptors, and its ligand substance P, in the development of colitis downstream from mast cell activation.
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PMID:Beneficial effect of tachykinin NK1 receptor antagonism in the development of hapten-induced colitis in mice. 1694 72

Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal mast cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal mast cells by investigating the effects of NO synthase (NOS) inhibitors and a mast cell stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of mast cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent mast cell activation.
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PMID:Modulatory effect of nitric oxide on mast cells during induction of dextran sulfate sodium colitis. 1716 Apr 77

Mast cells were described by Erhlich at the end of XIX-th century. Their role was deeply investigated in asthma and allergy. The massive degranulation of mast cells in allergy can lead to anaphylactic shock. Recently, mast cells have been recognized again as a very interesting topic for investigation, due to their possible role in chronic inflammation. Moreover, through adenosine receptors, mast cells can be activated or inactivated. That is why these cells are regarded as a potential target of new drugs. It has been reported, that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. The intensification of ROS production may be measured by the level of carbonyl groups, as a marker of protein peroxidation. However, the role of mast cells in other than asthma diseases with chronic inflammation needs further investigation. It was found out that the information about mast cell distribution in colonic mucosa may serve as help in differentiation between inflammatory bowel disease and collagenous colitis. Moreover, its accumulation in focal active gastritis was confirmed in patients with Crohn's disease. An important role in regulation of inflammatory process seems to be reserved for adenosine receptors present on mastocytes. The activation of mast cells through the adenosine receptor is connected with 11-8 release, which stimulate the migration of leukocytes and oxidation reactions. The detection of mast cells in tissues should not be limited only to the simple histologic examination. It should be completed by the detection of products of degranulation, e.g. tryptase. This is the way to find out their actual function and state of activation.
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PMID:[Mast cells, their adenosine receptors and reactive oxygen species in chronic inflammatory pathologies of childhood]. 1720 8

Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.
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PMID:Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1. 1763 Oct 2

It has been suggested but not proven that hypersensitivity type I reactions are involved in the pathogenesis of canine inflammatory bowel disease (IBD). The main effector cells in type I hypersensitivity reactions are mast cells (MCs). Canine MCs, as human MCs, can be subdivided into three subtypes according to their content of mast cell-specific proteases: tryptase (MCT), chymase (MCC), or tryptase and chymase bearing MCs (MCTC). In this study, numbers and subsets of mast cells were investigated in biopsies from the gastrointestinal tract of dogs with histopathologically confirmed lymphocytic-plasmacytic enteritis (LPE) (n=4), lymphocytic-plasmacytic colitis (LPC) (n=1) and eosinophilic gastroenterocolitis (EGE) (n=11). Paraffin sections of formalin-fixed samples from the stomach, small intestine (duodenum, jejunum, ileum) and colon were stained by using a metachromatic staining method (kresylecht-violet; KEV) and a combined enzyme histochemical and immunohistochemical technique for chymase and tryptase. Additionally, immunohistochemistry with antibodies against T cells (CD3), macrophages (myeloid/histiocyte antigen) and IgA, IgG and IgM bearing cells was conducted. Quantitative evaluation of mast cells and semiquantitative scoring of immunohistochemically stained cells were performed. Between the two histopathologically defined groups clear differences concerning mast cell numbers were detected. In most affected intestinal tissue locations of dogs with LPE/LPC a decrease in metachromatically (kresylecht-violet) stained granule-containing MCs and immunohistochemically stained MCT,C,TC was found. This reduction could be due to mast cell degranulation, a T helper cell 1 dominated reaction pattern or a "thinning out" due to increasing T cells, IgA and IgG bearing cells. Dogs with EGE displayed higher variability in mast cell numbers but most of the affected large and small intestinal locations had increased numbers of MCs. In these cases, T cells, IgA bearing cells and macrophages also increased. Increased numbers of MCs and eosinophils seen in the intestinal mucosa of dogs with EGE could indicate the presence of a type I hypersensitivity reaction (T helper cell 2 pattern) in response to dietary antigens. Changes in cell numbers occurred also in unaffected locations of dogs with LPE/LPC and EGE which showed reduced MCT,C,TC, increased KEV positive cells and partially increased leucocytes and macrophages.
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PMID:Characterization of mast cell numbers and subtypes in biopsies from the gastrointestinal tract of dogs with lymphocytic-plasmacytic or eosinophilic gastroenterocolitis. 1785 Aug 82

Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.
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PMID:Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. 1805 23

Nerve growth factor (NGF) is a neurotrophin implicated in intestinal pathophysiology, such as impaired barrier function, altered motility and a lowered threshold to noxious stimuli in colitis. We evaluated the cellular source of NGF and determined the effect of inflammation on its expression in TNBS-induced colitis in the rat. Receptors for NGF were studied by immunocytochemistry, showing that submucosal neurons expressed both trkA and p75(NTR). NGF presence and activity was assessed by bioassay, ELISA, western blotting and immunocytochemistry. Bioassay of colonic mucosa using the PC12 cell line showed low levels in control tissue but a marked increase in NGF activity with inflammation. Western blotting showed the appearance of 13 kDa NGF in inflamed mucosa by 6 h, declining over time to become similar to control by 35 days. Semi-quantitative PCR showed minimal mRNA for NGF in control mucosa that increased sharply by 6 h post-TNBS. Laser-capture microdissection was used to collect colonic epithelial cells, where mRNA for NGF was markedly increased by 6 h post-TNBS. While the epithelium of the inflamed colon was positive for NGF by immunocytochemistry, other cell types remained negative. A potential precursor form of NGF, but not 13 kDa NGF itself, was detected in several epithelial cell lines and a mucosal mast cell line. We conclude that NGF is principally synthesized by epithelial cells in the inflamed colon, where the presence of specific receptors suggests the potential for wide-spread action.
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PMID:Inflammation causes expression of NGF in epithelial cells of the rat colon. 1837 96

Recent studies showed that enteric helminth infection improved symptoms in patients with inflammatory bowel disease as well as in experimental models of colitis. The aim of this study was to determine the mechanism of the protective effect of helminth infection on colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral infection of Heligmosomoides polygyrus third-stage larvae, were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion. Expression of cytokines was assessed by quantitative real-time PCR, and mast cells were visualized by immunohistochemistry. TNBS-induced colitis induced mucosal damage, upregulated Th1 cytokines, and depressed secretory responses. Heligmosomoides polygyrus elevated Th2 cytokine expression, increased mast cell infiltration and mucosal resistance, and also reduced some secretory responses. Prior H. polygyrus infection prevented TNBS-induced upregulation of Th1 cytokines and normalized secretory responses to specific agonists. TNBS-induced colitis did not alter H. polygyrus-induced mast cell infiltration or upregulation of Th2 cytokine expression. The results indicate that the protective mechanism of enteric nematode infection against TNBS-induced colitis involves prevention of Th1 cytokine expression and improved colonic function by a mechanism that may involve mast cell-mediated protection of neural control of secretory function. Similar response patterns could account for the clinical improvement seen in inflammatory bowel disease with helminthic therapy.
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PMID:Anti-Inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. 1864 79

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.
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PMID:Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. 1893 52

The present study was designed to investigate the ameliorative potential of Punica granatum in dextran sulfate sodium (DSS) induced ulcerative colitis. DSS (2%) was administered orally in drinking water for 7 days to induce ulcerative colitis. The extent and severity of ulceration was analysed macroscopically, histopathologically and using a disease activity index. Myeloperoxidase (MPO), a specific marker of inflammation; histamine, a marker of mast cell degranulation; superoxide anion generation and, lipid peroxides were analysed. Administration of DSS resulted in a significant development of ulceration in the colon along with a rise in histamine, MPO activity and oxidative stress. Treatment with Punica granatum extract and its ellagic acid rich fraction (100 mg/kg and 200 mg/kg p.o.) significantly attenuated DSS-induced colonic inflammation along with attenuation of histamine, MPO and oxidative stress. The antiulcerative effect of Punica granatum extract and its ellagic acid rich fraction were comparable to sulphasalazine (100 mg/kg, p.o.) and sodium cromoglycate (40 mg/kg i.p). It is concluded that Punica granatum has a potential for ameliorating DSS-induced colitis and its ellagic acid rich fraction may be responsible for this effect. Further, the antiulcerative effects may be attributed to mast cell stabilizing, antiinflammatory and antioxidant actions.
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PMID:Exploring the ameliorative potential of Punica granatum in dextran sulfate sodium induced ulcerative colitis in mice. 1936 59


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