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

To investigate human synovial mast cell physiology, we developed a model in which mast cells in human synovial explant cultures were activated by immunologic or non-immunologic mechanisms. Small (3 mm) cubes of synovial membrane were incubated with or without secretagogue for 30, 45 or 60 min, and supernatant histamine concentrations were quantified. We measured significant histamine release with compound 48/80 at concentrations > or = 1 mg/ml, and with calcium ionophore A23187 at > or = 5 micrograms/ml. Rabbit IgG anti-human IgE induced significant histamine release at all concentrations tested, maximum at 78 micrograms/ml. Morphine sulfate produced no histamine release from synovial explants, in contrast to its significant stimulation of histamine release from neonatal foreskin explants in our explant system. We confirmed synovial mast cell degranulation by electron microscopy, and showed that it corresponded with measurable histamine release. Furthermore, histamine release was not due to secretagogue-induced cytotoxicity, as assessed by supernatant lactate dehydrogenase levels and by ultrastructural analysis. Since morphine sulfate induces mast cell degranulation and histamine release in adult and neonatal human skin, our data show that although synovial and dermal mast cells have a similar granule enzyme profile and electron microscopic morphology, they differ in functional responses. These observations support recent data that among similar human mast cell subtypes there are physiologic differences. Finally, our explant model will be useful in studies of mast cell involvement in arthritis.
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PMID:Mast cell activation in human synovium explants by calcium ionophore A23187, compound 48/80, and rabbit IgG anti-human IgE, but not morphine sulfate. 882 77

It has been reported that the administration of interferon alpha-2b is of potential benefit in the treatment of mastocytosis based on a single patient study (NEJM, Feb 27, 1992, 326(9):619-623). Following this report, we administered interferon alpha-2b at a dose of 4 to 5 million units per square meter of body surface area for at least 12 months to one patient with mastocytosis with an associated hematologic disorder (patient 1), one patient with aggressive systemic mastocytosis (patient 2), and one patient with indolent mastocytosis (patient 3). Patients were monitored with the following clinical and laboratory parameters: serial bone marrow biopsies and aspirates, patient log of histamine release attacks, medication dependency, plasma tryptase levels, serum lactate dehydrogenase (LDH) levels, white blood cell counts and differentials, extent of urticaria pigmentosa lesions, bony involvement, and extent of gastrointestinal involvement and hepatomegaly. We also examined the ability of interferon alpha-2b to inhibit recombinant human stem cell factor (rhSCF)-dependent mast cell proliferation from CD34+ bone marrow-derived cells. All patients demonstrated continued progression of disease in one or more clinical criteria at one year of therapy. Similarly, interferon alpha-2b did not inhibit the culture of mast cells from CD34+ bone marrow-derived cells in the presence of SCF. Thus, in our study of three patients with systemic mastocytosis, treatment with interferon alpha-2b was found to be ineffective in controlling progression of disease.
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PMID:Treatment of three patients with systemic mastocytosis with interferon alpha-2b. 888 64

In the present study, the possible role of mast cells in ischemia/reperfusion-induced myocardial injury was evaluated in the isolated 'mast cell depleted' rat heart. Hearts isolated from sensitized and non-sensitized rats were perfused according to Langendorff. After 30 min of normoxic perfusion, hearts were challenged with antigen, a procedure which is known to result in a massive mast cell degranulation in sensitized hearts. After another 20 min, both 'mast cell depleted' and control hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. The release of lactate dehydrogenase (LDH) was determined, to quantitate the extent of irreversible injury of cardiomyocytes. Histamine release was measured to establish mast cell degranulation. Coronary flow (CF) and left ventricular developed pressure (LVDP) were monitored to study the consequences of the procedures on hemodynamic recovery. It was found that both CF and LVDP significantly increased during the first min after antigen challenge. These changes were accompanied by an almost complete degranulation of cardiac mast cells. The increase in CF and LVDP values were rapidly followed by a decrease, reaching minimal values of 159 +/- 4% and 85 +/- 4% of those before administration of antigen, respectively, at 2-3 min after antigen challenge. No effect of antigen challenge on LDH release were found indicating that mast cell degranulation did not compromise myocyte integrity. During reperfusion following 30 min of ischemia both the increase in CF and LVDP in 'mast cell-depleted' hearts were not significantly different from those in control (non-sensitized) hearts. Similarly, at the end of the reperfusion-phase, CF and LVDP values in sensitized hearts were comparable to those in control hearts. Reperfusion results in increased LDH release, which at no point in time was significantly different between sensitized and non-sensitized hearts. In non-sensitized hearts histamine release during the reperfusion phase was not detectable. Therefore, the results indicate that in the isolated rat heart, mast cells are most likely not involved in acute ischemia/reperfusion-induced myocardial injury.
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PMID:Antigen-evoked mast cell degranulation in the isolated rat heart: no effect on subsequent ischemia-reperfusion induced damage. 908 42

Our study was designed to investigate the role of resident cardiac mast cells in the cardioprotective effect of ischemic preconditioning. Ischemic/compound 48/80 preconditioning and treatment with compound 48/80, a mast cell degranulator (1 microg/ml), produced cardioprotective and antiarrhythmic effects in isolated perfused rat heart subjected to 30-min global ischemia followed by 30-min reperfusion. Four episodes of ischemic/compound 48/80 preconditioning and compound 48/80 treatment markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary perfusate and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia or fibrillation (VT/VF) during the reperfusion phase. The release of mast cell peroxidase (MPO), a marker of mast cell degranulation in coronary perfusate, increased immediately after ischemic and compound 48/80 preconditioning. The cardioprotective and antiarrhythmic effect of ischemic/compound 48/80 preconditioning was lost within 60 min. It is proposed that the cardioprotective effect of ischemic preconditioning, which lasts for 60 min in isolated rat heart, may be ascribed to degranulation of resident cardiac mast cells.
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PMID:Resident cardiac mast cells and the cardioprotective effect of ischemic preconditioning in isolated rat heart. 926 40

The present study was designed to investigate the effect of amiloride, a Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning in isolated rat heart. Four episodes of ischaemic preconditioning and amiloride (174 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and infarct size in hearts subjected to 30 min of global ischaemia followed by 120 min of reperfusion. Amiloride (174 microM) administered during ischaemic preconditioning (Amiloride in Ischaemic Preconditioning), produced no marked effect on LDH and CK release and infarct size. Ischaemic preconditioning and amiloride treatment significantly reduced ischaemia/reperfusion induced release of mast cell peroxidase (MPO). Four episodes of pH (20 mm of ammonium chloride) preconditioning also produced cardioprotection and decreased ischaemia/reperfusion induced release of MPO. It is interesting to note that a significant increase in release of MPO was observed immediately after ischaemic preconditioning and the release was inhibited by amiloride. Moreover, similar increase in MPO release was noted immediately after pH preconditioning. These findings tentatively suggest that ischaemic preconditioning and pH preconditioning produced cardioprotective effect by activating Na+/H+ exchange and consequent degranulation of resident cardiac mast cells. Amiloride administered during ischaemic preconditioning attenuated the cardioprotective effect of ischaemic preconditioning.
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PMID:Effect of amiloride A Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning: possible involvement of resident cardiac mast cells. 934 36

To clarify the process of post-translational modification of L-histidine decarboxylase (HDC), we investigated the conversion of the 74-kDa form of HDC into the 53-kDa form in specialized organella of a rat basophilic/mast cell line (RBL-2H3). With treatment of streptolysin-O, RBL-2H3 cells released approximately 40% of HDC activity accompanied by over 90% of lactate dehydrogenase activity. Only the 74-kDa form of HDC was detected in the leaked fraction by SDS-polyacrylamide gel electrophoresis. The 74-kDa form in the homogenate of pulse-labeled cells was recovered in both the supernatant and particulate fractions, while the 53-kDa form was detected only in the particulate fraction containing marker proteins of microsomes, Golgi, and lysosomal granules. Confocal microscopic observation using double staining immunofluorescence with anti-GST fusion HDC antiserum showed that most of the HDC coexists with protein-disulfide isomerase, a typical marker of the luminal space of the ER. With treatment of digitonin, RBL-2H3 cells released only 74-kDa HDC. Trypsin digestion of digitonin-permeabilized cells resulted in the disappearance of the 74-kDa form but not the 53-kDa form. From these results, it is assumed that the 74-kDa form of HDC, synthesized in the cytosol, is translocated into the lumen of the ER, where it is converted to the 53-kDa form.
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PMID:Intracellular localization of the 74- and 53-kDa forms of L-histidine decarboxylase in a rat basophilic/mast cell line, RBL-2H3. 952 22

This study was designed to investigate the effect of disodium cromoglycate (DSCG), a mast cell stabilizer, on cardioprotective effect of ischemic preconditioning. Isolated rat heart was subjected to 30 min of global ischemia followed by 30 min of reperfusion. Ischemic preconditioning was provided by four episodes of 5-min global ischemia followed by 5 min of reperfusion before sustained ischemia. Ischemic preconditioning and DSCG (10 and 100 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during reperfusion. Ischemic preconditioning and DSCG treatment also significantly reduced ischemia/reperfusion-induced mast cell peroxidase (MPO) release, a marker of mast cell degranulation. A significant increase in MPO release was observed immediately after ischemic preconditioning, and the release was found to be inhibited in hearts perfused with DSCG (10 and 100 microM) during ischemic preconditioning. DSCG administered during ischemic preconditioning (DSCG in ischemic preconditioning) attenuated the cardioprotective and antiarrhythmic effects of ischemic preconditioning. DSCG in ischemic preconditioning produced no marked effect on ischemia/reperfusion-induced MPO release. These findings tentatively suggest that DSCG administration during ischemic preconditioning abolishes its cardioprotective effect, perhaps by stabilizing resident cardiac mast cells.
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PMID:Cardiac mast cell stabilization and cardioprotective effect of ischemic preconditioning in isolated rat heart. 959 79

The present study was designed to investigate the role of adrenergic component and cardiac mast cell degranulation in the cardioprotective effect of ischaemic preconditioning. Isolated rat hearts were subjected to 30 min of global ischaemia followed by 30 min of reperfusion. Ischaemic/norepinephrine (100 microm) preconditioning markedly reduced ischaemia-reperfusion-induced release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Moreover, ischaemic/norepinephrine preconditioning significantly reduced ischaemia-reperfusion-induced release of mast cell peroxidase (MPO), a marker of mast cell degranulation. Prazosin (0.1 microm), a alpha(1)adrenoceptor blocker, administered during ischaemic/norepinephrine preconditioning attenuated the cardioprotective and antiarrhythmic effect of ischaemic/norepinephrine preconditioning. MPO release increased immediately after ischaemic/norepinephrine preconditioning and the release was found to be inhibited in hearts subjected to ischaemic/norepinephrine preconditioning in the presence of prazosin. However, prazosin (0.1 microm) treatment per se produced cardioprotective and antiarrhythmic effects and reduced ischaemia-reperfusion-induced MPO release. These findings tentatively suggest that ischaemic preconditioning produced cardioprotective and antiarrhythmic effect by activating alpha(1)adrenoceptors and consequent degranulation of cardiac mast cells. Prazosin administered during ischaemic preconditioning abolished its ameliorative effect.
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PMID:Possible role of adrenergic component and cardiac mast cell degranulation in preconditioning-induced cardioprotection. 1043 71

Our study is designed to correlate nitrite concentration, an index of nitric oxide (NO) release with mast cell peroxidase (MPO), a marker of cardiac mast cell degranulation and cardioprotective effect of ischaemic preconditioning in isolated perfused rat heart subjected to 30 min of global ischaemia and 30 min of reperfusion. Ischaemic preconditioning, comprised of four episodes of 5 min global ischaemia and 5 min of reperfusion, markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and incidence of ventricular premature beats (VPBs) and ventricular tachycardia and fibrillation (VT/VF) during reperfusion phase. Ischaemia-reperfusion induced release of MPO was markedly reduced in ischaemic preconditioned hearts. Increased release of nitrite was noted during reperfusion phase after sustained ischaemia in preconditioned hearts as compared to control hearts. No alterations in the release of nitrite was observed immediately after ischaemic preconditioning. However, ischaemic preconditioning markedly increased the release of MPO prior to global ischaemia. It is proposed that cardioprotective and antiarrhythmic effect of ischaemic preconditioning may be ascribed to degranulation of cardiac mast cells. Depletion of cytotoxic mediators during ischaemic preconditioning and consequent decreased release of these mediators during sustained ischaemia-reperfusion may be associated with preservation of structures in isolated rat heart responsible for NO release.
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PMID:Possible role of cardiac mast cell degranulation and preservation of nitric oxide release in isolated rat heart subjected to ischaemic preconditioning. 1054 45

To determine the role of mast cells in ischaemia-reperfusion (IR) injury to skeletal muscle, W(f)/W(f) mast cell-deficient and their corresponding wild-type mice were subjected to 70 min tourniquet ischaemia and 24 h reperfusion. As measured by nitroblue tetrazolium (NBT) staining, muscle viability was 9% in wild-type and 94% in mast cell-deficient animals (p<0.001). Assay of residual lactate dehydrogenase activity within the injured muscle (p<0.05) and histological examination confirmed the greater muscle necrosis in treated wild-type than in treated mast cell-deficient mice. There was no significant difference in the degree of neutrophil infiltration, tissue myeloperoxidase content or water content of IR-injured muscle in the two mouse phenotypes. To determine further the role of mast cells in IR injury, wild-type mice were treated 30 min prior to reperfusion with an intraperitoneal dose of either saline or the mast cell-stabilizing agent lodoxamide trometamol (2.5, 7.5, 25 or 75 mg/kg). Twenty-four hours after removal of the tourniquet, saline-treated gastrocnemius muscle had a mean viability of 14% compared with 28% (p<0.05) and 48% (p<0.01) after 25 mg/kg and 75 mg/kg of lodoxamide treatment, respectively. The ability of lodoxamide to stabilize mast cells was confirmed by histological examination. Ischaemic muscle reperfused for 1 h showed much less degranulation of mast cells in mice pretreated with lodoxamide (50 mg/kg) than in saline-treated controls. These findings suggest that mast cells are a major source of mediators of necrosis in IR injury to skeletal muscle.
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PMID:The role of mast cells in ischaemia-reperfusion injury in murine skeletal muscle. 1091 20


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