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)

Experiments were carried out to provide evidence of the effect of L-arginine (L-Arg), its analogue NG-monomethyl-L-arginine (MeArg) and of some nitrovasodilators (sodium nitroprusside, NaNP; 3-morpholino-sydnonimine, SIN-1) which spontaneously release nitric oxide (NO) on ischemia-reperfusion injury, histamine release and mast cell degranulation, occurring after multiple ligature and release of the left anterior descending (LAD) coronary artery in isolated perfused guinea-pig hearts. The reopening of the LAD coronary artery leads to a release of histamine related to a decrease in microdensitometry of cardiac mast cells and to calcium overload. The perfusion of the heart with NO-donors significantly reduces either the release of histamine, the loss of mast cell metachromasia and the overload of calcium. These effects were potentiated by SOD. The results suggest that the endogenous formation of NO and molecules able to generate NO have a role in the prevention of post-ischemic tissue injury.
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PMID:The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart. 171 36

The complete amino-acid sequence of the copper-zinc superoxide dismutase of the Photobacterium leiognathi was determined. The fragmentation strategy employed included cyanogen bromide cleavage at its methionine residues and the only tryptophan residue. The S-carboxymethylated chain was further cleaved by means of trypsin, in order to obtain overlapping fragments. For sequence determination automated solid or liquid-phase techniques of Edman degradation were used. C-Terminal amino acids of the entire chain were determined after treatment with carboxypeptidase A. Comparison of the primary structure of this bacterial Cu-Zn superoxide dismutase with the established amino-acid sequences of the other eukaryotic Cu-Zn superoxide dismutases revealed clear homologies. Correspondingly, the Cu-Zn-binding amino-acid residues of the active centre were localized: His45, His47, His70, His79, His125 and Asp91. The two cysteine residues in position 52 and 147 were homologous to the cysteine residues, modelling the essential intrachain disulfide bridge of the corresponding bovine enzyme. As only 25-30% of aligned sequence positions were found to be identical, the enzyme of P. leiognathi shows only a remote phylogenetic relationship towards eukaryotic Cu-Zn superoxide dismutases. When compared to the established phylogenetic tree of the cytochrome c family, this indicates a separate evolution of Cu-Zn superoxide dismutase in Photobacterium. Therefore, a natural gene transfer from the eukaryotic host (ponyfish) to the prokaryotic photobacterium, which Martin and Fridovich postulated 1981 (J. Biol. Chem. 256, 6080-6089) on the basis of amino-acid compositions, can be excluded.
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PMID:The primary structure of Cu-Zn superoxide dismutase from Photobacterium leiognathi: evidence for a separate evolution of Cu-Zn superoxide dismutase in bacteria. 688 93

The exposure of the macrophage cell line, J774 to mast cell granules (MCG) led to the formation of altered nuclear transcription factor proteins (NF-kappaBx), which had faster electrophoretic mobility than the p50 homodimer of NF-KB, but retained comparable DNA binding capacity. Antibodies to N-terminal peptides of p50, p52, p65 or c-Rel supershifted only a fraction of NF-kappaBx. Western blot analyses revealed that nuclear p65 and c-Rel were progressively degraded after exposure to MCG, whereas nuclear p50 appeared to be unaffected. In contrast, cytoplasmic p50, p65, c-Rel as well as IkBalpha remained intact after MCG treatment, although p52 was clearly degraded. In comparison to J774 cells, incubation of mouse peritoneal macrophages with MCG resulted in more extensive alterations to NF-KB proteins. The alterations in NF-KB proteins did not affect the expression of inducible nitric oxide synthase (iNOS) or TNF-alpha mRNA inJ774 cells. These data indicate that exposure of J774 cells to MCG leads to generation of altered nuclear p52, p65 and c-Rel, which retain intact N-terminal peptides, specific oligonucleotide binding and transactivating activity. On the other hand, in peritoneal macrophages, MCG induce more extensive modifications to NF-KB proteins with associated inhibition of iNOS or TNF-alpha mRNA expression.
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PMID:Transient degradation of NF-kappaB proteins in macrophages after interaction with mast cell granules. 992 32

Thermal trauma has a direct effect on mast cells, triggering the secretion of histamine. This secretion leads to an enhanced xanthine oxidase activity and an increased production of reactive oxygen species (ROS), the latter being produced after burns through differing mechanisms. As ROS have been shown to have deleterious effects on cellular membranes, a lesion of the mast cell membrane could close the circle of autoinjury due to the vasoactive actions of mast cell mediators. Our studies were designed to assess the potentiality of ROS as stimulators of mast cell degranulation after burns by comparing two groups of rats treated, respectively, with SOD and saline solution after a scald injury. Plasma levels of tryptase and histamine were analyzed as markers of mast cell activity. A comparison of the mean increases of tryptase between baseline and 3-h postburn levels in the two groups shows significant differences (p < 0.001) (control: 0.13+/-0.04, SOD: 0.03+/-0.01). When comparing the mean increases between the baseline and 3 h postburn levels of histamine in the two groups, significant differences were also found (p < 0.001) (control group: 2.70+/-0.57. SOD group: 1.22+/-0.32). The lower levels of histamine and tryptase induced by SOD provides indirect evidence that ROS are involved in the process, causing the release of such mediators by mast cells, which may in turn suggest that ROS can act as stimulators of mast cell degranulation in burns.
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PMID:Role of mast cells in the pathogenesis of postburn inflammatory response: reactive oxygen species as mast cell stimulators. 1071 57

Murine gp49, a 49-kDa type I transmembrane glycoprotein, is a member of the Ig-like receptors expressed on the surface of cells involved in natural immunity such as mast cells, NK cells, and macrophages. The two major subtypes, gp49A and gp49B, are encoded by two different genes adjacent to each other. gp49B contains an immunoreceptor tyrosine-based inhibitory motif in its cytoplasmic region and is known to function as an inhibitory molecule. In contrast, gp49A does not harbor any specific motif for signal transduction, nor has its physiological role been determined. Here we report on the stimulatory nature of gp49A by analyzing biochemical characteristics of chimeric molecules consisting of an ectodomain of Fc receptor and a C-terminal half of gp49A, namely the pretransmembrane, transmembrane, and cytoplasmic portions, expressed on the rat basophilic leukemia mast cell line. Cross-linking of the chimeric receptors evoked cytoplasmic calcium mobilization, PGD(2) release, and transcription of IL-3 and IL-4 genes, but did not elicit degranulation of the cells. The chimeric molecule could be expressed as a singlet and a homodimeric form on the cell surface. A pretransmembrane cysteine residue of gp49A was necessary for dimer formation. Dimerization was be necessary for their incorporation into glycolipid-enriched membrane fraction (GEM) upon cross-linking stimuli. The calcium mobilization response was inhibited by treatment of cells with methyl-beta-cyclodextrin, an inhibitor of GEM formation. Together with these results, it was strongly suggested that gp49A could be expressed as a homodimer and elicit activation signals that lead to calcium mobilization, eicosanoid production, and cytokine gene transcription through its incorporation into GEM.
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PMID:Stimulatory function of gp49A, a murine Ig-like receptor, in rat basophilic leukemia cells. 1104 24

1. Myocardial injury caused by ischaemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, mast cell activation, and peroxidation of cell membrane lipids. These events are followed by myocardial cell alterations resulting eventually in cell necrosis. An enhanced formation of reactive oxygen species is widely accepted as a stimulus for tissue destruction and cardiac failure. 2. In this study, we have investigated the cardioprotective effects of M40403 in myocardial ischaemia-reperfusion injury. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Ischaemia was induced in rat hearts in vivo by ligating the left anterior descending coronary artery. Thirty minutes after the induction of ischaemia, the ligature was removed and reperfusion allowed to occur for at least 60 min. M40403 (0.1-1 mg kg(-1)) was given intravenously 15 min before ischaemia. 3. The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose-dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post-reperfusion of the ischaemic myocardium was also reduced by M40403. 4. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P-selectin and for anti-intercellular adhesion molecule (ICAM-1) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in these tissues. No staining for nitrotyrosine, P-selectin or ICAM-1 was found in cardiac tissue taken at the end of the ischaemic period. 5. Overall, M40403 treatment reduced the morphological signs of myocardial cell injury and significantly improved survival. 6. Taken together, these results clearly indicate that M40403 treatment exerts a protective effect against ischaemia-reperfusion-induced myocardial injury, supporting a key role for superoxide anion in reperfusion injuries. This suggests that synthetic enzymes of SOD such as M40403, offer a novel therapeutic approach for the treatment of ischaemic heart disease where superoxide anion plays a dominant role.
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PMID:Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo. 1211 Jun 15

Activins, members of the transforming growth factor-beta (TGF-beta) superfamily, are potent growth and differentiation factors. Our previous studies revealed that activin A, a homodimer of inhibin/activin beta(A), was induced in mast cells and peritoneal macrophages in response to their activation. In the present study, we examined the roles of activin A in murine bone marrow-derived, cultured mast cell progenitors (BMCMCs), which expressed gene transcripts for molecules involved in activin signaling, suggesting that BMCMCs could be target cells of activin A. Treatment of activin A inhibited 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide uptake into BMCMCs in a dose-dependent manner. The IC(50) concentration was 2.1 nM, which was less potent than 185 pM TGF-beta(1). Activin A treatment caused morphological changes toward the differentiated cells at 2 nM and up-regulated mRNA of mouse mast cell protease-1 (mMCP-1), a marker enzyme of mature mucosal mast cells, at 1 nM. Activin A also showed activity in inducing migration of BMCMCs; the optimal concentration for maximal migration was 10 pM, which was much lower than the concentrations to inhibit cell growth and to activate the mMCP-1 gene. Taking the present results together with our previous results, it is suggested that activin A secreted from activated immune cells recruits mast cell progenitors to sites of inflammation and that with increasing activin A concentration, the progenitors differentiate into mature mast cells. Thus, activin A may positively regulate the functions of mast cells as effector cells of the immune system.
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PMID:Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. 1277 12

The cross-linking of FcepsilonRI on mast cells by IgE and antigen (Ag) initiates activation cascades that lead to allergic responses. FcepsilonRI is composed of an alpha and a Beta monomer, and a gamma homodimer, and the Beta and gamma chains possess immunoreceptor tyrosine-based activation motifs (ITAMs). Through the phosphorylation of ITAMs, activation signals are transmitted intracellularly. Mast cells are also activated through FcgammaR-FcRgamma by an immune complex, which often results in hypersensitivity. We defined FcRgamma-signal-dependent and -independent mast cell responses by analyzing FcRgamma-/- mice reconstituted with mutant FcRepsilon-ITAM. Most of the FcepsilonRI-mediated activations by IgE(+Ag), such as induction of degranulation, arachidonic acid metabolism, cytokine production and systemic anaphylaxis, are dependent on signaling through FcRgamma-ITAM. On the other hand, IgE without Ag induces the upregulation of surface FcepsilonRI expression and mast cell survival. The former is independent of and the latter is dependent on FcRgamma-ITAM. As a molecular mechanism for the generation of diverse responses through FcepsilonRI, we found that the quantity and the duration of the FcRgamma signal determine the degranulation and the survival of mast cells, respectively. Furthermore, such a sustained FcRgamma-signal-induced survival is mediated by autocrine cytokine production. In this review, the in vivo function of FcRgamma and the signal regulation for the distinct responses of mast cells through FcepsilonRI are discussed.
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PMID:Regulation of mast cell activation through FcepsilonRI. 1610 60

This study intended to examine the effect of 3,4-dihydroxy-phenyl lactic acid (DLA), a major ingredient of Salvia miltiorrhiza, on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory injury. DLA (5 mg.kg(-1).h(-1)), superoxide dismutase (SOD, 12,000 U.kg(-1).h(-1)), or catalase (CAT, 20 mg/kg) was continuously infused either starting from 10 min before the ischemia or 10 min after the initiation of reperfusion. The venule diameter, number of adherent leukocytes, FITC-albumin leakage, dihydrorhodamine 123 fluorescence, and mast cell degranulation were determined using an intravital microscope. The production of hydrogen peroxide (H(2)O(2)) and the expression of adhesion molecules CD11b/CD18 in neutrophils were evaluated by in vitro experiments. The results showed that pretreatment with DLA significantly reduced peroxide production in and leukocyte adhesion to venular wall, albumin leakage, and mast cell degranulation induced by I/R. The DLA posttreatment exerted an ameliorating effect on I/R-induced disorders as well, characterized by inhibiting further increase in peroxide production in venular wall and albumin leakage and diminishing the number of leukocytes that had adhered to the venular wall. In vitro experiments revealed that treatment with DLA significantly attenuated TNF-alpha plus fMLP-evoked production of H(2)O(2) and the H(2)O(2)-elicited expression of CD11b/CD18 on neutrophils. SOD and CAT manifested similarly but with the exception that either SOD or CAT were unable to retrieve the adherent leukocytes if administrated after initiation of reperfusion and to depress the H(2)O(2)-induced expression of CD11b/CD18 on neutrophils. It is concluded that DLA protects from and ameliorates the I/R-induced microcirculatory disturbance by interfering with both peroxide production and adhesion molecule expression.
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PMID:Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery. 1900 40

Atrial fibrillation (AF) is a common arrhythmia that increases the risk of stroke and heart failure. Here, we have shown that mast cells, key mediators of allergic and immune responses, are critically involved in AF pathogenesis in stressed mouse hearts. Pressure overload induced mast cell infiltration and fibrosis in the atrium and enhanced AF susceptibility following atrial burst stimulation. Both atrial fibrosis and AF inducibility were attenuated by stabilization of mast cells with cromolyn and by BM reconstitution from mast cell-deficient WBB6F1-KitW/W-v mice. When cocultured with cardiac myocytes or fibroblasts, BM-derived mouse mast cells increased platelet-derived growth factor A (PDGF-A) synthesis and promoted cell proliferation and collagen expression in cardiac fibroblasts. These changes were abolished by treatment with a neutralizing antibody specific for PDGF alpha-receptor (PDGFR-alpha). Consistent with these data, upregulation of atrial Pdgfa expression in pressure-overloaded hearts was suppressed by BM reconstitution from WBB6F1-KitW/W-v mice. Furthermore, injection of the neutralizing PDGFR-alpha-specific antibody attenuated atrial fibrosis and AF inducibility in pressure-overloaded hearts, whereas administration of homodimer of PDGF-A (PDGF-AA) promoted atrial fibrosis and enhanced AF susceptibility in normal hearts. Our results suggest a crucial role for mast cells in AF and highlight a potential application of controlling the mast cell/PDGF-A axis to achieve upstream prevention of AF in stressed hearts.
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PMID:Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts. 2003 2


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