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)

Increased mast cell numbers and mast cell activation represent one of the prevalent etiologic theories for interstitial cystitis, an inflammatory condition in the bladder. This study was designed primarily to determine whether increased mast cell tryptase in the bladder wall may play a role in activating bladder endothelial cell phospholipase A(2) (PLA(2)), leading to increased inflammatory phospholipid metabolite accumulation, which may propagate the inflammatory process. We stimulated human bladder microvascular endothelial cells with thrombin or tryptase and measured the activation of PLA(2) and the production of multiple membrane phospholipid-derived inflammatory mediators. Thrombin and tryptase stimulation resulted in activation of a Ca(2+)-independent PLA(2), leading to increased release of arachidonic acid and prostacyclin and increased production of platelet-activating factor. These responses were blocked completely by pretreatment of human bladder microvascular endothelial cells with the Ca(2+)-independent PLA(2)-selective inhibitor bromoenol lactone. The combination of increased prostacyclin and platelet-activating factor in the bladder circulation may result in vasodilation and increased polymorphonuclear leukocyte adherence to the endothelium and may facilitate recruitment of polymorphonuclear leukocytes to the bladder wall of patients with interstitial cystitis.
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PMID:Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells. 1556 75

A unique combined mastocytoma-junctional nevus presented as a 4-mm dark brown macule in the axilla of a 57-year-old white female. Histopathologic examination revealed a proliferation of mast cells partially or completely filling the dermal papillae, hyperpigmentation of the basal keratinocytes and mildly increased basal melanocytes. Overlying the mast cell proliferation, pigmented junctional nevus nests were present. The mast cells were strongly positive with Giemsa stain and mast cell tryptase immunohistochemical stain; nevomelanocytic cells were negative. Nevomelanocytes were strongly immunoreactive for S100, HMB-45, Mart-1, and tyrosinase; mast cells were negative. The clinicopathologic features suggested a synchronous proliferation of 2 cell types in the same small cutaneous field rather than a collision tumor. While the cutaneous mast cells probably originated as a disseminated clone, it is postulated that local mast cell growth factor induced nevomelanocytic proliferation and modulated mast cell growth. In fact, the tumor exhibited strong immunoreactivity for the mast cell growth factor receptor (CD117) in mast cells, basal melanocytes, and nevus nests. The incidence of dual mast cell-melanocytic tumors appears to be very low, as only 3 total cases have now been reported. However, since in patients with multiple mastocytomas only a small fraction of lesions are biopsied, the true incidence may be higher than supposed.
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PMID:Combined mastocytoma-junctional nevus. 1561 30

Tryptase is a neutral protease of human mast cells, and an important indicator of mast cell activation and degranulation in anaphylactic events. The elevation of serum mast cell tryptase (SMCT) is used for postmortem diagnosis of anaphylaxis. We have quantified the SMCT levels of 122 forensic autopsy cases with various causes of death and found only three where the SMCT levels were remarkably elevated, with values of 179, 68.9 and 69.4 ng/ml (normal level <13.5 ng/ml). The three cases were suspected to have suffered from hyperthermia, and the deaths did not seem to be related to causes of death where SMCT levels have been reported to be elevated in some cases. Two cases were patients who had been prescribed long-term neuroleptics or antidepressants, and myoglobin was detected immunohistochemically in the renal tubules of both cases. The other case died of heatstroke. A possible mechanism of hyperthermia in SMCT elevation is discussed.
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PMID:Three cases of suspected hyperthermia with remarkable elevation of serum mast cell tryptase. 1573 10

Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium of rats. In this study our purpose was to determine how the central histaminergic system, which controls excitability and neurotransmitter release through G-protein coupled receptors, is affected by the pathophysiology of traumatic brain injury. We found that mast cell infiltration, as a result of the trauma, occurred primarily in the injured cortex and did not proceed beyond the fimbria of the hippocampus. In comparing injured animals with controls we found that H3 receptor binding densities are significantly decreased bilaterally in the cortex but are significantly increased bilaterally in the thalamus. H3 receptor binding densities may well be affected by mast cell secretion of mediators (i.e. histamine, heparin, leukotrienes), evidenced by detection of a cosecreted enzyme (mast cell tryptase) in the extracellular region. Moreover, we detected significant decreases in H1 and H3 receptor mRNA as well as Cu/Zn-dependent superoxide dismutase (SOD) mRNA in the thalamic region closest to the trauma. These significant decreases delineate the extent of cellular damage because of trauma and may underlie sustained cognitive and motor deficits displayed by these animals.
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PMID:Traumatic brain injury results in mast cell increase and changes in regulation of central histamine receptors. 1577 8

Tight junctions between intestinal epithelial cells prevent ingress of luminal macromolecules and bacteria and protect against inflammation and infection. During stress and inflammation, mast cells mediate increased mucosal permeability by unknown mechanisms. We hypothesized that mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability. Colonocytes expressed PAR2 mRNA and responded to PAR2 agonists with increased [Ca2+]i. Supernatant from degranulated mast cells increased [Ca2+]i in colonocytes, which was prevented by a tryptase inhibitor, and desensitized responses to PAR2 agonist, suggesting PAR2 cleavage. When applied to the basolateral surface of colonocytes, PAR2 agonists and mast cell supernatant decreased transepithelial resistance, increased transepithelial flux of macromolecules, and induced redistribution of tight junction ZO-1 and occludin and perijunctional F-actin. When mast cells were co-cultured with colonocytes, mast cell degranulation increased paracellular permeability of colonocytes. This was prevented by a tryptase inhibitor. We determined the role of ERK1/2 and of beta-arrestins, which recruit ERK1/2 to PAR2 in endosomes and retain ERK1/2 in the cytosol, on PAR2-mediated alterations in permeability. An ERK1/2 inhibitor abolished the effects of PAR2 agonist on permeability and redistribution of F-actin. Down-regulation of beta-arrestins with small interfering RNA inhibited PAR2-induced activation of ERK1/2 and suppressed PAR2-induced changes in permeability. Thus, mast cells signal to colonocytes in a paracrine manner by release of tryptase and activation of PAR2. PAR2 couples to beta-arrestin-dependent activation of ERK1/2, which regulates reorganization of perijunctional F-actin to increase epithelial permeability. These mechanisms may explain the increased epithelial permeability of the intestine during stress and inflammation.
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PMID:Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. 1602 50

The pruritogenic potency of tryptase and its involvement in anti-pruritic effect of intravenous nafamostat mesilate (NFM) were studied in mice. An intradermal injection of tryptase (0.05-1 ng/site) elicited scratching in ICR mice, while chymase was without effects at doses of 0.05-50 ng/site. The dose-response curve of tryptase action was bell-shaped and the effect peaked at 0.1 ng/site (approximately 0.7 fmol/site). NFM (10 mg/kg) inhibited scratching induced by tryptase but not by histamine and serotonin. NFM (1-10 mg/kg) produced the dose-dependent inhibition of scratching induced by intradermal compound 48/80 (10 microg/site). The inhibition by NFM (10 mg/kg) was abolished in mast cell-deficient (WBB6F1 W/W(V)) mice, but not in wild-type (WBB6F1 +/+) mice. NFM (10 mg/kg) suppressed tryptase activity in the mouse skin. Proteinase-activated receptor-2 (PAR-2) neutralizing antibody (0.1 and 1 microg/site) and the PAR-2 antagonist FSLLRY (10 and 100 microg/site) inhibited scratching induced by tryptase (0.1 ng/site) and compound 48/80 (10 microg/site). These results suggest that mast cell tryptase elicits itch through PAR-2 receptor and that NFM inhibits itch-associated responses mainly through the inhibition of mast cell tryptase.
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PMID:Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. 1635 60

In 1960, a trypsin-like activity was found in mast cells [Glenner GG & Cohen LA (1960) Nature 185, 846-847] and this activity is now commonly referred to as 'tryptase'. Over the years, much knowledge about mast cell tryptase has been gathered, and a recent (18 January 2006) PubMed search for the keywords 'tryptase + mast cell*' retrieved 1661 articles. However, still very little is known about its true biological function. For example, the true physiological substrate(s) for mast cell tryptase has not been identified, and the potential role of tryptase in mast cell-related disease is not understood. Mast cell tryptase has several unique features, with perhaps the most remarkable being its organization into a tetrameric state with all of the active sites oriented towards a narrow central pore and its consequent complete resistance towards endogenous macromolecular protease inhibitors. Much effort has been invested to elucidate these properties of tryptase. In this review we summarize the current knowledge of mast cell tryptase, including novel insights into its possible biological functions and mechanisms of regulation.
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PMID:Biology of mast cell tryptase. An inflammatory mediator. 1664 May 53

Among the intestinal tumors of hematopoietic cell origin, lymphoma is the most common in the dog. Herein, we characterized the clinical and pathologic features of 11 dogs (average age, 10.6 +/- 2.5 years) with T-cell lymphoma of the intestinal tract with eosinophil infiltrates. No sex predominance was apparent. All had localized tumor masses in the small intestine. Grossly, the intestinal wall was thickened, and the lumen of the affected intestine was usually narrowed. Microscopically, we observed transmural diffuse invasion of round to pleomorphic tumor cells. Tumor cells showed varying morphology, from scanty to abundant cytoplasm, and round to ovoid nuclei with scattered to dense chromatin. In seven of the dogs, tumor cells had infiltrated into the epithelium. All showed infiltration of eosinophils and all 11 tumors had a T-cell phenotype (CD3+, CD79-). Only one tumor stained positive for the mast cell marker c-kit and none was positive for mast cell tryptase. We did not observe ultrastructurally apparent granules in any of the tumor cells. These results suggest that, in dogs, T-cell lymphomas of intestinal origin resemble mast cell tumors of intestinal origin with respect to cell structure and eosinophil infiltration. Therefore, in the absence of epitheliotropism, it is difficult to confirm the differential diagnosis without immunostaining for mast cell and lymphocyte markers, including mast cell tryptase, c-kit, CD3, and CD79.
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PMID:T-cell lymphoma with eosinophilic infiltration involving the intestinal tract in 11 dogs. 1667 80

The distribution profile of infiltrated mast cell-subpopulations and eosinophils in the lung and heart sections of the patients who died of severe allergic hyperresponsiveness, was investigated. Four study groups were designed comprising 9 cases who died in systemic anaphylaxis (Group I), 10 asthmatic individuals whose death were assigned to acute and severe bronchial asthma (Group II), 10 asthmatic cases who died from non-immunological diseases (Group III). Twenty consecutive autopsies of non-allergic subjects who died of unnatural causes (Group IV) served as control group in this study. Utilizing antibodies against human tryptase and chymase and a double immunohistochemical staining method, we distinguished successfully all three subsets of mast cells (MC), MC-TC (containing both tryptase and chymase), MC-T (containing only tryptase) and MC-C (containing only chymase) types, subdivided on the basis of the protease compositions of their secretory granules. In order to immunostaining eosinophils, we used antibody to major basic protein as a marker. We also measured postmortem blood tryptase, specific and total serum IgE. The intriguing finding of this study was the marked differences of cellular composition in the lung between fatal anaphylaxis and asthma death. Significant augmentation of MCs infiltrated in lung and heart sections of anaphylaxis patients and drastic infiltration of bronchial eosinophils in asthmatic death and consequent release of their related inflammatory mediators might explain the differential expression of the associated symptoms in these two groups. The anaphylactic deaths did show neither emphysema nor significant mucous bronchial secretions whereas all asthmatic deaths did. The degree of pulmonary congestion and edema was also more severe in anaphylaxis. This corresponded with the histological findings and the location and number of mast cell-subsets and eosinophils in the different compartments of the lungs. We have demonstrated that the third type of mast cell MC-C is only found in the lungs in anaphylactic deaths. The practical consequence of our study will be that it is now possible to confirm a suspicion of anaphylaxis death not only by measurements of serum mast cell tryptase, but also by immunohistochemical methods.
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PMID:Differential accumulation of pulmonary and cardiac mast cell-subsets and eosinophils between fatal anaphylaxis and asthma death: a postmortem comparative study. 1708 16

Mast cells are involved in inflammatory processes and in allergic reactions where immunologic stimulation leads to degranulation and generation of numerous cytokines and inflammatory mediators. Mast cells have been proposed as an immune gate to the brain, as well as sensors of environmental and emotional stress, and are likely involved in neuropathologic processes such as multiple sclerosis. Among mast cell products, the protease tryptase could be associated with neurodegenerative processes through the activation of specific receptors (PARs) expressed in the brain, while interleukin (IL)-6 likely causes neurodegeneration and exacerbates dysfunction induced by other cytokines; or it could have a protective effect against demyelinisation. In this report we show that quercetin, a natural compound able to act as an inhibitor of mast cell secretion, causes a decrease in the release of tryptase and IL-6 and the down-regulation of histidine decarboxylase (HDC) mRNA from human mast cell (HMC)-1 cells. As quercetin dramatically inhibits mast cell tryptase and IL-6 release and HDC mRNA transcription by HMC-1 cell line, these results nominate quercetin as a therapeutical compound in association with other therapeutical molecules for neurological diseases mediated by mast cell degranulation.
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PMID:Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. 1719 Nov 6


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