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)

A patient is reported with mast cell infiltration of the small intestine in the absence of the skin involvement characteristic of mast cell disease. She also had subtotal villous atrophy responsive to a gluten-free diet. Criteria for diagnosing mast cell disease of the small intestine are proposed. The literature of small intestinal mast cell disease is reviewed and the relationship to coeliac disease is discussed.
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PMID:Involvement of the small intestine in systemic mast cell disease. 0 Feb 73

The gastrointestinal tract is a rich source of mast cells with an enormous surface area that permits a high degree of interaction between the mast cell and intestinal luminal contents. The active metabolic products of the mast cell influence gastrointestinal secretion, absorption, and motility through paracrine effects of local mast cell degranulation and also cause systemic effects through the release of cellular products into the blood stream. Systemic mastocytosis influences physiologic function through the systemic effects of mast cell products released from focal (e.g., bone marrow) or wide spread increases in mast cell number. Local gastrointestinal proliferation of mast cells in response to recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter gastrointestinal function and induce systemic symptoms. Celiac sprue, inflammatory bowel disease, and non-ulcer dyspepsia are three examples of gastrointestinal diseases in which mast cells can be implicated in the pathophysiology of the symptoms.
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PMID:The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. 200 61

To study mast cell, basophil, and eosinophil populations within celiac sprue mucosae in comparison with various disease-control specimens, toluidine blue-stained 1-micron plastic sections were analyzed morphometrically by light microscopy. Within lamina propria of celiac sprue mucosae each population of cells was markedly expanded and fell to control levels during gluten restriction. Changes within surface and crypt epithelium, however, were not significantly different from those in the severer, "flat" disease-control lesions, and were not affected by gluten restriction. Basophils were not identified within surface or crypt epithelium of any specimen analyzed. The influx of eosinophils and basophils into lamina propria occurred by emigration via pericryptal venules. Mature mast cells were not seen within the microvasculature, neither were these cells undergoing mitosis: thus their origin was from unidentified precursors. The gluten-dependent alterations in each of these cell populations in celiac sprue mucosae are consistent with secondary effector mechanisms, probably resulting from cell-mediated reactions that occur primarily within the lamina propria, rather than the epithelium.
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PMID:Inflammatory component of celiac sprue mucosa. I. Mast cells, basophils, and eosinophils. 240 59

Coeliac disease is a malabsorptive disorder caused by intolerance to gluten and is characterized by a remodelling of the intestinal mucosa including villus atrophy, crypt hyperplasia and net increase of mucosal volume. Changes of the number of mucosal mast cells (MMCs) in coeliac mucosa has recently been reported, suggesting that the mast cell activity could have a pathogenetic role in gluten enteropathy. MMCs located solely in the lamina propria are the main repository for small-gut mucosal histamine. A consecutive prospective study was designed to study the histamine content, MMC numbers, and the relative volume of lamina propria in intestinal biopsies from adult patients suffering from unexplained diarrhea and/or malnutrition. Histamine was measured by a HPLC-method, the number of MMC was counted after long toluidine-blue staining, and the relative volumes of lamina propria and epithelium were estimated morphometrically. The findings were correlated to the histopathological appearance of the mucosa. As compared to controls the histamine content increased by 80% and MMC numbers by about 60% in the coeliac mucosa. There was also a correlation between MMC numbers and histamine content for both normal and coeliac mucosae (r = 0.81). The morphometric estimation of the relative volumes of epithelium and lamina propria revealed that the lamina-propria compartment was increased by approximately 40% in coeliac mucosa. Taking the changes in compartmental volumes of the remodelled coeliac mucosa into account, our results suggest that the histamine content and MMC population were significantly increased. MMC and MMC-associated histamine may therefore be involved in the pathogenesis of gluten enteropathy.
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PMID:Histamine and mucosal mast cells in gluten enteropathy. 372 11

A study of mast cell content of the small intestinal mucosa in children with celiac disease is presented. Twenty patients with true celiac disease were studied and compared with 7 patients with transient gluten intolerance and 20 normal control patients. In healthy children we found (mean +/- SE) 142.5 +/- 16.4 mast cells/mm2. In children with active celiac disease, only 40.1 +/- 19.5 cells were found. This difference was highly significant (P less than 0.001). On a gluten-free diet for 1.5 years, the number of mast cells was 82.2 +/- 27.2/mm2 and still remained significantly depressed (P less than 0.001). Upon gluten challenge in celiac disease, the numbers fell to 58.3 +/- 32.6/mm2, while in transient gluten intolerance the numbers of mast cells attained were 102.5 +/- 22.5/mm2, near normal values. These findings indicate that during the untreated phase of celiac disease the number of mast cells is depressed. On a gluten-free diet, the number rises but does not reach normal control levels even after prolonged remission. It is suggested that even during remission of celiac disease the mast cells continue to be damaged by unidentified toxic agents.
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PMID:Intestinal mast cells in different stages of celiac disease. 374 85

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors.
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PMID:Human intestinal mucosal mast cells: expanded population in untreated coeliac disease. 682 6

There have frequently been doubts as to the relevance of food allergy, in particular as far as the involvement of the intestinal tract is concerned. Several studies, however, have confirmed the existence of allergic reactions in the gut, with an estimated prevalence of about 1-2% in adults. Clinical symptoms are unspecific and include nausea, vomiting, abdominal pain, cramping and diarrhea. Intestinal mast cells, as well as intestinal eosinophils, have been shown to be involved in the pathogenesis of food-allergy-related enteropathy. In addition to classical IgE-dependent degranulation, further agonists have been demonstrated for mast cell activation, for example IL-4. The methods used to confirm the diagnosis of intestinal allergy are still insufficient. Until now, blinded oral challenge procedures with food antigens have been accepted as the 'gold standard' in diagnosing food allergy, although these tests have practical problems. Therefore, new test systems have been developed, such as endoscopic provocation tests, that may improve diagnostic procedures. Elimination diet still presents the main basis of therapy. Aspects to be focused on in the future are the role fo IgE-independent allergic mechanisms in intestinal allergy, the impact of cross-reactivity with other allergens and the relationship to other inflammatory bowel diseases such as Crohn's disease, ulcerative colitis, celiac disease and irritable bowel syndrome.
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PMID:Allergy and the gut. 1082 17

The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.
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PMID:New insights into the autoantibody-mediated mechanisms of autoimmune bullous diseases and urticaria. 1646 21

The gastrointestinal tract is a rich source of mast cells with an enormous surface area that permits a high degree of interaction between the mast cell and intestinal luminal contents. The active metabolic products of the mast cell influence gastrointestinal secretion, absorption, and motility through paracrine effects of local mast cell degranulation and also cause systemic effects through the release of cellular products into the blood stream. Systemic mastocytosis influences physiologic function through the systemic effects of mast cell products released from focal (e.g., bone marrow) or wide spread increases in mast cell number. Local gastrointestinal proliferation of mast cells in response to recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter gastrointestinal function and induce systemic symptoms. Celiac sprue, inflammatory bowel disease, and non-ulcer dyspepsia are three examples of gastrointestinal diseases in which mast cells can be implicated in the pathophysiology of the symptoms.
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PMID:The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. 1679 7

Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-alpha transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling.
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PMID:n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells. 1694 31


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