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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophil peroxidase (EPO) and to a lesser degree neutrophil peroxidase (myeloperoxidase, MPO) bound tightly to mast cell granules (MCG), particularly when the latter were depleted of histamine by suspension in physiologic salt solutions. The bound EPO was localized on the surface of the granule, and its dissociation required salt concentrations of high enough ionic strength (greater than 0.75 M) to solubilize the MCG matrix. Elution of MPO from the complex occurred at a lower salt concentration. The MCG/EPO complex retained the capacity of the isolated EPO to catalyze the iodination reaction when supplemented with iodide, H2O2, and a protein acceptor and to kill microorganisms when supplemented with H2O2 and a halide (iodide, chloride). Indeed, the MCG/EPO complex had significantly greater iodinating and bactericidal activity than the free enzyme when standardized to equal guaiacol units of peroxidase activity. Thus, in areas of inflammation where mast cells and phagocytic leukocytes coexist, there is the potential for the formation of active complexes extracellularly between mast cell granules and molecules such as EPO (or MPO) that can affect the inflammatory response.
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PMID:Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity. 698 10

The growing recognition of asthma as an immunologic disease mediated by inflammatory cells and mediators has changed the nature of therapy and monitoring of this disease. Modulation of inflammatory mediators such as leukotrienes, prostaglandins, and adenosine by specific immunoregulatory pharmacotherapy is now becoming well-recognized as essential for proper management of allergic diseases, including asthma. The newly-developed immunoassays for specific inflammatory cell activation markers, such as tryptase for mast cell activation, myeloperoxidase for neutrophil activation, and eosinophilic cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) for eosinophil activation, may significantly enhance the ability to both determine the cellular etiology of allergic inflammation and also to monitor the efficacy of antiinflammatory therapies in suppressing cell-specific immunologic events.
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PMID:Introduction: mediator assays and inflammatory events in asthma and allergic disease (Immunology Research Institute of New England Symposium). 792 8

Several lines of evidence document a critical role for mast cells in immune complex-mediated inflammatory models. However, their role in nonimmune models of acute inflammation is largely unknown. In the present investigation, the role of mast cells was examined in calcium ionophore (A23187)-induced mouse peritoneal inflammation. Intraperitoneal injection of A23187 (20) micrograms/mouse) elicited marked and transient increases in immunoreactive levels of 6-ketoprostaglandin-F2 alpha, leukotrienes B4, C4, D4, E4, and F4. There were no discernible differences in levels of these mediators in male Swiss Webster mice, mast cell-deficient mice (WBB6F1-W/W'), and age-matched controls (WBB6F1-+/+), suggesting a minimal role of mast cells in eicosanoid biosynthesis in this model. However W/W' mice showed smaller increases in levels of myeloperoxidase, a marker for neutrophils, compared to +/+ mice. Both W/W' and +/+ mice have lower constitutive levels of peritoneal N-acetyl-beta-D-glucosaminidase (NAG), a marker for mononuclear cells. Similar to the changes seen in myeloperoxidase, W/W' mice exhibited a blunted NAG response compared to +/+ mice. These results suggest that mast cell products other than eicosanoids may contribute to the changes in cellular trafficking in response to intraperitoneal A23187. These results also suggest that mast cells are required for full expression of inflammatory responses.
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PMID:Role of mast cells in calcium ionophore (A23187)-induced peritoneal inflammation in mice. 807 Sep 2

The objective of this study was to determine whether ischemia-reperfusion (I/R) of the small bowel activated mast cells and, if so, to determine whether this event contributed to granulocyte infiltration and mucosal barrier dysfunction. Autoperfused segments of the jejunum were exposed to 30 min of ischemia followed by 60 min of reperfusion. Epithelial permeability was assessed by the clearance of 51Cr-labeled EDTA from plasma to lumen. Plasma rat mast cell protease II (RMCP II) was measured and used as an index of mucosal mast cell degranulation, whereas myeloperoxidase (MPO) activity was used as an index of granulocyte infiltration. I/R caused a significant increase in plasma RMCP II levels, MPO activity, and epithelial permeability. The mucosal mast cell stabilizer doxantrazole prevented the I/R-induced increase in all three parameters. The connective tissue mast cell stabilizer ketotifen had no effect. To determine whether oxidants were involved in mast cell degranulation, some animals were pretreated with superoxide dismutase and catalase. This regimen completely abolished the I/R-induced rise in plasma RMCP II levels and attenuated mucosal MPO activity and epithelial permeability. Selective inhibitors of two mast cell-derived mediators, platelet-activating factor and histamine, did not attenuate the rise in epithelial permeability. These data suggest that oxidant-induced mucosal mast cell degranulation is a key event in the granulocyte infiltration and tissue dysfunction associated with reperfusion of the ischemic intestine.
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PMID:Mast cells contribute to ischemia-reperfusion-induced granulocyte infiltration and intestinal dysfunction. 807 30

The effects of topical application of arachidonic acid (AA) or phorbol ester, tetradecanoylphorbol 13-acetate (TPA), on edema response, vascular permeability, MPO, NAG, and generation of eicosanoids were studied in two murine models of cutaneous inflammation. AA produced a short-lived edema response with a rapid onset that was associated with marked increases in levels of prostaglandins (PGE2, 6-keto-PGF1 alpha, PGF2 alpha), thromboxane B2 (TxB2) and leukotriene B4 (LTB4), with smaller increases in levels of LTC4. TPA produced a longer-lasting edema that was associated with marked influx of neutrophils and predominant formation of LTB4 along with significant changes in levels of TxB2. Circulating T lymphocytes have no apparent role in the acute inflammatory responses induced by either agent. Arachidonic acid-induced vascular permeability preceded the edema response and neutrophil influx, whereas TPA-induced vascular permeability paralleled the edema response and influx of neutrophils. Mast cells appear to be important in the complete expression of inflammatory response, i.e., edema, cellular influx, and vascular permeability induced by either AA or TPA, as these responses were blunted in mast cell-deficient mice. Inhibitors of CO or 5-LO attenuated inflammatory responses in both models. The LTB4 receptor antagonist, SC-41930, inhibited the inflammatory response to TPA but had little effect on that initiated by AA. This suggests that LTB4 is an important mediator in the phorbol ester-induced inflammatory response, whereas peptidoleukotrienes and prostaglandins regulate vascular permeability responses in the arachidonate model.
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PMID:Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. 811 31

Mast cell hyperplasia and changes in phenotypic characteristics subsequent to myenteric and extrinsic denervation of a segment of rat jejunum were studied. The myenteric plexus and extrinsic nerves were ablated by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride. There was a four-fold increase in the number of mast cells in the smooth muscle layers 15 days after denervation. This increase was sustained for at least 90 days after treatment. No increase in mast cell number was observed in the villus-crypt axis of the jejunum. Berberine sulfate fluorescent detection of heparin-containing mast cells demonstrated that a change in mast cell phenotype occurred between 20 and 90 days after the denervation procedure. The fact that myeloperoxidase activity was the same in denervated and control tissue within 5 days of denervation demonstrates the lack of a chronic inflammatory reaction. Our results suggest that mast cells might play a role in the gut wall re-modeling processes.
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PMID:Proliferation of mast cells in the smooth muscle of denervated rat jejunum. 828 47

Anti-inflammatory properties have been ascribed to a series of N-(fluorenyl-9-methoxycarbonyl) amino acids called leumedins that inhibit the activity of granulocytes and T-lymphocytes. We evaluated one of these leumedins, N-(fluorenyl-9-methoxycarbonyl) leucine (NPC 15199), in a model of ileitis in guinea pigs. Ileitis was induced by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol) in anesthetized guinea pigs. NPC 15199 was administered daily (10 or 100 mg/kg, s.c.). After 7 days, the guinea pigs were anesthetized, and saline was administered intraluminally into an ileal loop created at the site of TNBS administration and was withdrawn after 30 min. The changes in lavage protein, nitrite levels, myeloperoxidase (MPO) activity and mast cell numbers were used as indices of inflammation and injury. NPC 15199 (10 or 100 mg/kg) attenuated or abolished TNBS-induced elevations in lavage protein and nitrite content. Only the high dose of NPC 15199 (100 mg/kg) attenuated ileal MPO activity and mast cell hyperplasia. Histological disturbances induced by TNBS administration included crypt hypertrophy, mucosal and submucosal fibrosis and smooth-muscle hyperplasia. These disturbances were reversed by high-dose NPC 15199 (100 mg/kg) but were minimally affected by low-dose NPC 15199 (10 mg/kg). We conclude that NPC 15199 prevents mucosal injury and dysfunction in this model of intestinal inflammation. Inhibition of granulocyte infiltration does not appear to be essential for the beneficial effects of NPC 15199 and suggests that the alternative actions of NPC 15199 may be pertinent to this model.
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PMID:Guinea pig ileitis is attenuated by the leumedin N-(fluorenyl-9- methoxycarbonyl)-leucine (NPC 15199). 839 62

Changes in the populations of neurotransmitter receptors involved in the control of intestinal smooth muscle function have been associated with the altered motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced gut inflammation is accompanied by an increase in alpha- and a decrease in beta-adrenoceptor numbers in guinea pig small intestine. In the present study, we investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS-induced adrenoceptor changes. Smooth muscle adrenoceptor populations, labelled by subtype-specific radioligands 6 days after TNBS, were significantly different from those of sham-treated controls: alpha 1- and alpha 2-adrenoceptor numbers increased by more than 50%, while beta-adrenoceptor numbers decreased by more than 50%. These changes, associated with severe inflammation as assessed histologically and by myeloperoxidase assay, were prevented by doxantrazole or L-NAME, and only partly by MK-886. In contrast, indomethacin did not prevent these changes. It appears then that: (a) mast cell mediators, nitric oxide and leukotrienes are likely to contribute to TNBS-induced changes in adrenoceptor populations in the guinea pig inflamed intestine; (b) there is no evidence for prostanoid involvement in this process. It was suggested that changes in smooth muscle adrenoceptor populations may be an important mechanism by which gut inflammation alters intestinal motility.
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PMID:Evidence for mast cell, leukotriene and nitric oxide involvement in the regulation of the adrenoceptor number of inflamed small intestine in guinea pigs. 853 63

To date, the diagnosis of mast cell disease (MCD) relied on routine plus histochemical stains. Its differential diagnosis, however, includes a variety of other hematopoietic and particularly B-cell lymphoid neoplasms that are best identified in paraffin sections using immunostains. To determine the paraffin-section immunoreactivity of MCD, 20 specimens from 14 patients with MCD and 1 bone marrow sample (from a patient with probable MCD) that showed equivocal metachromasia, were stained with antitryptase, CD68 (KP-1), CD20 (L26), antilysozyme, and antimyeloperoxidase antibodies. Ten hairy cell leukemias (HCLs), six lymphomas of parafollicular and/or monocytoid B-cell (MBCLs) and low-grade mucosa-associated lymphoid tissue (MALT) types, six granulocytic sarcomas, and five acute myeloid leukemias with monocytic differentiation (M4 and M5 types) were also stained. Tryptase positivity was identified in all of the MCD cases. The staining was moderate to strong in 20 of the 21 specimens, including the probable MCD case. No other neoplasms tested were tryptase positive. CD68 showed similar to even stronger staining in all of the specimens of MCD, HCL, granulocytic sarcoma, and acute myeloid leukemia (M4 and M5 types) tested and in five of the six MBCL and/or MALT-type lymphomas. Weak-to-moderate lysozyme staining seemed to be present in at least 7 of the MCD specimens, whereas there was a lack of staining for myeloperoxidase in 12 specimens, and 7 specimens were nonevaluable (1 case was not tested). Myeloperoxidase was identified in all of the granulocytic sarcomas and acute myeloid leukemias (M4 and M5 types) but not in any HCLs, MBCLs, or low-grade lymphomas of MALT type. CD20 was negative in all of the MCD and myelomonocytic neoplasms but positive in all of the HCLs, MBCLs, and low-grade B-cell lymphomas of MALT type. MCD, therefore, has a characteristic tryptase-positive, CD68-positive, and CD20-negative phenotype in paraffin sections. This distinguishes MCD from the hematopoietic and/or lymphoid disorders that it most closely resembles.
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PMID:Immunohistochemical characterization of mast cell disease in paraffin sections using tryptase, CD68, myeloperoxidase, lysozyme, and CD20 antibodies. 890 35

The relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
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PMID:Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. 920 Oct 88


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