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

Mast cells (MC) are biochemically and functionally heterogeneous and the mixture of MC phenotypes varies according to anatomical location. Intestinal mucosal MC (IMMC) have been used to study the mucosal MC subset in the rat, but they are difficult to isolate in sufficient numbers and with consistent purity and viability. Bone marrow-derived MC (BMMC), with an apparent mucosal MC phenotype, can be cultured in large numbers and with high purity from normal rat bone marrow using supernatants from mesenteric lymph node cells of rats infected with the nematode, Nippostrongylus brasiliensis. We have compared serine proteinase content, tumour necrosis factor-alpha (TNF-alpha) storage and secretion, and TNF-alpha-dependent cytotoxicity of IMMC and BMMC to assess the appropriateness of BMMC as in vitro models of mucosal MC. Two-dimensional gel electrophoretic analysis revealed that the overall protein constituents of BMMC and IMMC were highly homologous. Immunoblotting confirmed that both MC types expressed the MMC-associated enzyme, rat mast cell proteinase-2 (RMCP-2), but not RMCP-1, mast cell proteinase-5 (MCP-5) or carboxypeptidase A (CPA), which characterize the connective tissue MC in the rat and which were detected in a representative of this subset, namely, the periotoneal MC (PMC). BMMC demonstrated levels of TNF-alpha-dependent cytotoxicity that were equivalent to those of IMMC. Like IMMC, BMMC contained little stored TNF-alpha, in comparison with PMC, but both MC types generated substantial amounts of TNF-alpha 6 hr following IgE-mediated activation. Pretreatment of PMC with recombinant rat interferon-gamma (IFN-gamma) for 20 hr inhibited anti-immunoglobulin E (anti-IgE)-mediated release of the granule-associated enzyme, beta-hexosaminidase, whereas identically treated BMMC were unresponsive to this cytokine. Similar results have previously been reported for IMMC. Rat BMMC, unlike their more immature and less phenotypically committed counterparts in the mouse, appear therefore to be more appropriate models for studies on the mucosal MC.
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PMID:Rat mucosal mast cells: the cultured bone marrow-derived mast cell is biochemically and functionally analogous to its counterpart in vivo. 965 26

The effects of a series of analogues of the antiallergic drug astemizole on the exocytosis of the enzyme beta-hexosaminidase were studied in a mast cell model, the rat basophilic leukemia (RBL-2H3) cell. Besides differences in the effects on Fc epsilonRI receptor-stimulated exocytosis, changes were also observed in Ca2+ influx and in the perturbation of the cell membrane. A strong correlation was found between the effects on antigen- and thapsigargin-stimulated 45Ca2+ influx. Furthermore, the inhibition of 45Ca2+ influx was correlated with the inhibition of beta-hexosaminidase release and membrane stabilization. It is concluded that the astemizole analogues are capable of inhibiting mast cell beta-hexosaminidase release through inhibition of Ca2+-store-operated Ca2+ channels (SOC). Compounds with high lipophilicity also released Ca2+ from intracellular stores. Lowering of the hydrophobicity by introduction of nitrogens or truncation at different sites in the astemizole structure decreased inhibitory activity on SOC channels. The inhibition of SOC channels cannot completely be ascribed to non-specific membrane effects. The piperidinyl-benzimidazole moiety was found to be important for inhibition of SOC channels. The observed differences in activity possibly depend on the way the compounds penetrate the membrane bilayer. Astemizole is an interesting new tool to study SOC channels and can be a lead for the design of mast cell-stabilizing antiallergic drugs.
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PMID:Structure-activity relationships of astemizole derivatives for inhibition of store operated Ca2+ channels and exocytosis. 969 27

The mast cell lines rat basophilic leukemia (RBL) and mouse C57 cells respond to IgE/antigen complexes by degranulation. Treatment of these cells with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), (10-100 nM) for 24-48 h enhanced IgE/antigen-induced exocytosis as monitored by release of hexosaminidase. A short term incubation with the hormone did not affect exocytosis, ruling out a rapid non genomic mechanism. The presence of vitamin D receptors, demonstrated by immunoblotting and the lack of effect of 24,25(OH)2D3 suggest a role for these receptors in the enhancing effect. 1,25(OH)2D3 also enhanced exocytosis induced by the calcium ionophore A23187 in the presence or absence of phorbol ester indicating modulation of events distal to signal transduction. 1,25(OH)2D3 enhanced exocytosis in the presence of cytochalasin D, indicating that the action of the hormone is not due to effects on microfilament structure. The results of this study suggest that 1,25(OH)2D3 may affect the allergic or pro-inflammatory potential of mast cells.
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PMID:1,25-Dihydroxyvitamin D3 enhances degranulation of mast cells. 978 2

Adenosine may play a role in asthma by enhancing inflammatory mediator release from lung mast cells. In this study, we investigated whether adenosine is released from cultured rat basophilic leukaemia (RBL-2H3) cells in response to antigen challenge and whether released adenosine enhances mediator release. RBL-2H3 cells closely resemble mucosal mast cells, the most common type of mast cell in lung tissue, and they express adenosine A3 receptors (which have been associated with asthma). Measurement of adenosine in RBL-2H3 cell incubation medium was possible if adenosine metabolism was inhibited by EHNA (10 microM; an adenosine deaminase inhibitor) and 5-iodotubericidin (5-IT; 10 microM; an adenosine kinase inhibitor). Basal adenosine concentration increased up to 1.0 microM during a 90 min incubation; after antigen challenge, adenosine concentration was increased by 0.3-0.4 microM above basal. Antigen-induced adenosine release ranged from 30-70 nmol/1.25x10(6) cells. Antigen-induced mediator release (beta-hexosaminidase and [3H]5-hydroxytryptamine) was increased by APNEA, an adenosine A3 receptor agonist (EC50 approximately 20 nm) but inhibited by EHNA and 5-IT, despite increased adenosine levels. This inhibition was not blocked by the adenosine A1/A2 receptor antagonist DPSPX (5 microM). Therefore, it is unlikely to be related to adenosine receptor activation. In conclusion, although our data provide no direct support for a positive feedback effect of adenosine on mast cell mediator release, the observation that IgE receptor stimulation increases adenosine production in cells which express stimulatory A3 receptors is consistent with this hypothesis.
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PMID:Evidence that IgE receptor stimulation increases adenosine release from rat basophilic leukaemia (RBL-2H3) cells. 980 62

Changes in farnesyl protein transferase (FPTase) activity and FPTase beta-subunit protein levels were determined in IgE-sensitized RBL-2H3 mast cells in response to polyvalent antigen administration. Ten minutes after the addition of DNP modified BSA to mast cells, whose high affinity receptor for IgE (FcvarepsilonRI) contained bound anti-DNP IgE, FPTase specific activity increased by 54 +/- 28%. Time course studies showed FPTase specific activity doubled during a 20- to 30-min period after antigen-induced cell aggregation. Also, an increase in FPTase beta-subunit protein during this time ( approximately 30%) was observed; this protein increase was not accompanied by a similar increase in FPTase beta-subunit m-RNA levels. The FcvarepsilonRI aggregation had no significant effect on the activities of other enzymes involved with farnesyl diphosphate (FPP) metabolism: FPP synthase, isopentenyl diphosphate isomerase, geranylgeranyl protein transferase, and squalene synthase. Specific inhibition of FPTase activity by manumycin was studied to determine what role FPTase plays in mast cell activation. Manumycin profoundly inhibited hexosaminidase release in activated cells, indicating FPTase is required for signal transduction involved with protein exocytosis from RBL-2H3 mast cells.
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PMID:Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced activation of RBL-2H3 mast cells. 1019 Sep 75

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.
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PMID:Role of mast cells as a trigger of inflammation in Helicobacter pylori infection. 1021 Jan 51

In this study, we have developed a method to obtain mast cells with connective tissue type mast cell (CTMC) characteristics directly from mouse bone marrow (BM) cells. BM cells were grown for 3 weeks in presence of interleukin-4 (IL-4) plus stem cell factor (SCF). SCF alone poorly supported growth and development of mast cells. IL-4 dose-dependently enhanced the expression of c-kit and high-affinity receptor for IgE (Fc(epsilon)RI) on the cell surface of SCF-cultured BM cells. Furthermore, cytoplasmic granulation and histamine synthesis of BM-derived mast cells were increased in presence of IL-4 and SCF. Histochemical staining demonstrated that granules were safranin positive. BM-derived mast cells could be activated for granule exocytosis (beta-hexosaminidase release) and lipid mediator generation (LTC4 production) via Fc(epsilon)RI after sensitization with IgE and subsequent crosslinking with multivalent antigen. In addition, mast cells derived from BM cells cultured with SCF plus IL-4 could be activated by substance P, a nonimmunologic stimulus, to release beta-hexosaminidase. The results presented indicate that IL-4 and SCF both have a prominent role in the development of mast cells from murine BM cells in vitro. Mast cells can directly be derived from BM cells in presence of SCF and IL-4 and the cultured cells show typical hallmarks of CTMC, indicating that precursor cells for CTMC may be present in BM. The described culture procedure may be useful to investigate the molecular aspects of the development of committed mast cell lineages.
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PMID:Stem cell factor and interleukin-4 induce murine bone marrow cells to develop into mast cells with connective tissue type characteristics in vitro. 1021 Mar 23

The A(3) adenosine receptor (A3AR) is one of four receptor subtypes for adenosine and is expressed in a broad spectrum of tissues. In order to study the function of A3AR, a mouse line carrying a mutant A(3) allele was generated. Mice homozygous for targeted disruption of the A3AR gene, A3AR(-/-), are fertile and visually and histologically indistinguishable from wild type mice. The lack of a functional receptor in the A3AR(-/-) mice was confirmed by molecular and pharmacological analyses. The absence of A3AR protein expression in the A3AR(-/-) mice was demonstrated by lack of N(6)-(4-amino-3-[(125)I]iodobenzyl)adenosine binding to bone marrow-derived mast cell membranes that were found to express high levels of A3AR in wild type mice. In A3AR(-/-) mice, the density of A(1) and A(2A) adenosine receptor subtypes was the same as in A3AR(+/+) mice as determined by radioligand binding to brain membranes. Additionally, A(2B) receptor transcript expression was not affected by ablation of the A3AR gene. A3AR(-/-) mice have basal heart rates and arterial blood pressures indistinguishable from A3AR(+/+) mice. Functionally, in contrast to wild type mice, adenosine and the A3AR-specific agonist, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-carboxamide (2-Cl-IB-MECA), elicit no potentiation of antigen-dependent degranulation of bone marrow-derived mast cells from A3AR(-/-) mice as measured by hexosaminidase release. Also, the ability of 2Cl-IB-MECA to inhibit lipopolysaccharide-induced tumor necrosis factor-alpha production in vivo was decreased in A3AR(-/-) mice in comparison to A3AR(+/+) mice. The A(2A) adenosine receptor agonist, 2-p-(2-carboxyethyl)phenylamino)-5'-N-ethylcarboxamidoadenosine, produced inhibition of lipopolysaccharide-stimulated tumor necrosis factor-alpha production in both A3AR(-/-) and A3AR(+/+) mice. These results show that the inhibition in vivo can be mediated by multiple subtypes, specifically the A(3) and A(2A) adenosine receptors, and A3AR activation plays an important role in both pro- and anti-inflammatory responses.
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PMID:Disruption of the A(3) adenosine receptor gene in mice and its effect on stimulated inflammatory cells. 1066 Jun 15

Genetic polyymorphisms that result in three amino acid changes in FcepsilonRI beta chain (Ile(181)-->Leu, Val(183)-->Leu, and Glu(237)-->Gly) have been identified as candidates that associate with allergic disorders such as atopy and asthma. To elucidate the biological significance of these polymorphisms in regulating the expression and function of FcepsilonRI, we generated four types of transfectants that express wild-type or mutant mouse beta chains corresponding to these human variants by retrovirus-mediated gene transfer into beta chain-deficient mouse-derived mast cells. No significant functional differences between the wild-type beta chain transfectant and any of the mutant beta chain transfectants were observed in beta-hexosaminidase release, intracellular calcium mobilization, or cytokine and leukotriene C(4) production in response to FcepsilonRI crosslinking. Our results suggest that these polymorphisms in FcepsilonRI beta chain do not affect FcepsilonRI-mediated mast cell activation at least in our mouse in vitro system.
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PMID:Polymorphisms in FcepsilonRI beta chain do not affect IgE-mediated mast cell activation. 1087 78

Cytosolic phospholipase A(2) (cPLA(2)) plays a critical role in mast-cell-related allergic responses [Uozumi, Kume, Nagase, Nakatani, Ishii, Tashiro, Komagata, Maki, Ikuta, Ouchi et al. (1997) Nature (London) 390, 618-622]. Bone-marrow-derived mast cells from mice lacking cPLA(2) (cPLA(-/-)(2) mice) were used in order to better define the role of cPLA(2) in the maturation and degranulation of such cells. Cross-linking of high-affinity receptors for IgE (FcepsilonRI) on cells from cPLA(-/-)(2) mice led to the release of negligible amounts of arachidonic acid or its metabolites, the cysteinyl leukotrienes and prostaglandin D(2), indicating an essential role for cPLA(2) in the production of these allergic and pro-inflammatory lipid mediators. In addition, the histamine content of the mast cells and its release from the cells were reduced to 60%. While these results are in agreement with a reduced anaphylactic phenotype of cPLA(-/-)(2) mice, the ratios of release of histamine and beta-hexosaminidase were, paradoxically, significantly higher for cells from cPLA(-/-)(2) mice than for those from wild-type mice. Consistently, IgE-induced calcium influx in mast cells was greater and more prolonged in cells from cPLA(-/-)(2) mice than in those from wild-type mice. Thus the loss of cPLA(2) not only diminishes the release of lipid mediators, but also alters degranulation. While the overall effect is still a decrease in the release of mast cell mediators, explaining the in vivo findings, the present study proposes a novel link between cPLA(2) and the degranulation machinery.
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PMID:Role of cytosolic phospholipase A2 in the production of lipid mediators and histamine release in mouse bone-marrow-derived mast cells. 1108 23


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