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)

Highly purified porcine phospholipase A2 induced noncytotoxic rat cell degranulation, as indicated by release of histamine without release of the cytoplasmic marker lactate dehydrogenase. Ultrastructural studies using transmission, scanning, and freeze fracture electron microscopic techniques indicated that phospholipase A2-induced degranulation was comparable to that caused by other mast cell secretagogues. Secretory changes noted were fusion of perigranular and plasma membranes, formation of vacuoles containing less electron-dense granules, and exocytosis of the altered granules through pores in the plasma membrane, without alteration in other intracellular organelles. The earliest consistent feature of the exocytotic process (within 1 minute) was the formation of plasma membrane bulges overlying cytoplasmic granules, with depletion of intramembranous particles from the bulges and a reduction in surface microridges. Phospholipase A2-induced mast cell degranulation was blocked by the phospholipase inhibitor 4-bromophenacyl bromide and by eicosa-5,8,11,14-tetraynoic acid (ETYA) but not by indomethacin. Since ETYA inhibits both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism and indomethacin only the cyclooxygenase pathway, these findings are compatible with the mediation of phospholipase A2-induced mast cell degranulation by a lipoxygenase product of the released arachidonic acid ETYA, however, may inhibit phospholipase activity directly and thus affect degranulation by phospholipase A2 in this way. These studies indicate that phospholipase A2 can induce mast cell degranulation and provides evidence that is compatible with, but not proof of, mediation of this process by a lipoxygenase product of arachidonic acid metabolism.
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PMID:Phospholipase A2-induced rat mast cell secretion. Role of arachidonic acid metabolites. 681 79

Cultured rat embryonic skin fibroblasts phagocytosed rat mast cell granules added to the medium or released from co-cultured mast cells by rabbit anti-rat IgE or Compound 48/80. Electron microscopy of fibroblasts incubated with mast cell granules revealed that granules adjacent to the plasmalemma were engulfed by long, thin cytoplasmic processes. Internalization proceeded to fusion of encircling processes and formation of phagosomes. Microtubules and 60 A microfilaments became closely associated with the phagosomal membrane to which small vesicles and cisternae of endoplasmic reticulum fused. The rate of uptake of mast cell granules by fibroblasts was dependent upon temperature and granule concentration. Cytochalasin B inhibited granule uptake whereas colchicine and nocodazole had little effect. Phagocytosis was not influenced by actinomycin D and cycloheximide, was partially inhibited by fluoride, and was markedly inhibited by cyanide, azide, and 2,4-dinitrophenol. Supernatants from fibroblast cultures incubated with mast cell granules for 24 and 48 hr, during which period phagocytosis occurred, contained elevated levels of collagenase and beta-hexosaminidase, but normal levels of lactate dehydrogenase and superoxide dismutase. These results support the concept that immediate hypersensitivity reactions are in part terminated by phagocytosis of biologically active discharged mast cell granules by resident connective tissue fibroblasts. Further, it is suggested that a consequence of this process is an alteration in fibroblast behavior, providing a unique link between immediate hypersensitivity reactions and connective tissue responses to inflammation.
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PMID:Phagocytosis of mast cell granules by cultured fibroblasts. 684 86

The authors describe the results of a series of cytochemical, autoradiographic, cytophotometric and immunological investigations carried out in a case of tissue mast cell leukaemia. Leukaemic mast cells showed certain distinctive cytochemical features, amongst which an intense periodic acid-Schiff (PAS) reaction, sensitive to amylase digestion, strong naphthol AS-D chloroacetate esterase (NASDCE), intense lactate dehydrogenase (LD) activity. Proliferative activity, determined autoradiographically with 3H-dT, was considerably low and was mainly confined to the larger cells. Also uridine and leucine incorporation were markedly reduced. Microdensitometry disclosed that the mast cell population was mainly arrested in the G1 phase. Because of previous attempts to destroy selectively neoplastic tissue mast cells with sheep antihuman IgE serum, a search for surface bound IgE was carried out, but gave a negative result. Possible therapeutic approaches are considered in the light of previous clinical experience and on the basis of the results of the kinetic and metabolic studies.
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PMID:Cytobiological and clinical aspects of tissue mast cell leukaemia. 737 28

Precooling of the tissues was investigated as a possible means of reducing the thermal damage during CO2 laser surgery of the oral mucosa. Standard wounds 5 mm long were created with the CO2 laser, with and without precooling, or the scalpel on the dorsum of tongues. Tissue damage was evaluated by studying changes in mast cells and in the activity of lactate (LDH) and succinate (SDH) dehydrogenase. Cooled unoperated tongues acted as controls. The area of thermal damage, indicated by loss of SDH activity, was significantly smaller in precooled tissues (p < 0.001). Although a similar pattern was detected using LDH, the difference was not significant. At both 0 and 6 h normal mast cell numbers were significantly different between groups (p < 0.02). Furthermore, at 0 time, there were significant differences in the numbers of degranulated mast cells between surgical treatment groups (p = 0.001), although not at 6 h. Total numbers of mast cells (normal and degranulated) did not differ between treatment groups or between 0 and 6 h sampling times. Positive significant correlations were observed between the cross-sectional areas and widths of non-reactive succinate and lactate dehydrogenase and the number of degranulated mast cells around the laser wounds. Analysis of the data demonstrated that (i) uncooled laser wounds but not precooled laser wounds were associated significantly with greater levels of immediate mast cell degranulation than scalpel wounds (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of thermal damage in precooled CO2 laser wounds using biological markers. 839 41

In the present study, we evaluated the potential role of mast cell degranulation in acute hypoxia/reoxygenation-induced injury to cardiomyocytes in the isolated rat heart. Histamine release was determined to delineate the extent of mast cell degranulation, whereas the release of creatine kinase (CK) and lactate dehydrogenase (LDH) was assessed to quantitate the extent of irreversible injury to cardiomyocytes. The suitability of peroxidase (PO) as a marker for mast cell degranulation was also evaluated. Reoxygenation resulted in a release of histamine corresponding with 6.5% +/- 0.6% of total tissue content, whereas LDH, CK and PO release amounted to 30% +/- 2%, 28% +/- 2% and 32% +/- 3% of their respective tissue contents. Identical perfusion in the presence of the mast cell stabilizer lodoxamide tromethamine resulted in a reduced histamine release (2.8% +/- 0.1%) of total tissue content upon reoxygenation, but the release of LDH, CK or PO was not influenced. Cumulative histamine release did not correlate with the amount of LDH, CK or PO released. Treatment with consecutive bolus injections of the mast cell degranulating compound 48/80 during normoxic perfusion resulted in an almost complete histamine release, whereas PO release remained below detection limit. When the compound 48/80-treated hearts were subjected to hypoxia/reoxygenation, the release of LDH, CK or PO during reoxygenation again remained unchanged, whereas histamine release was negligible. Determination of PO activity of freshly isolated cardiomyocytes demonstrated that the bulk of PO in rat hearts was located in this particular cell type. Therefore we conclude that in the isolated rat heart, PO release is not a specific marker of mast cell degranulation. In addition, our data provide no firm evidence that in this experimental model, mast cell degranulation contributes to a significant extent to acute hypoxia/reoxygenation-induced injury to cardiomyocytes.
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PMID:Lack of evidence for a role of mast cell degranulation in acute hypoxia/reoxygenation-induced injury in the isolated rat heart. 872 68

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


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