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

Activated mast cells (MC) can produce a wide variety of potent inflammatory mediators. Excessive alcohol consumption is known to lead to immune deficiency and propensity for pneumonias in particular. As MCs are important in the first line of defence of mucosal membranes we have studied the effect of ethanol (EtOH) on several MC functions. EtOH attenuated dose dependently IgE-induced degranulation of mouse bone marrow derived mast cells (mBMMC) as reflected by the release of granule associated beta-hexosaminidase (beta-hex). A mean of 26 +/- 7% inhibition of beta-hex release was observed in the presence of 5/1000 (86 mM) EtOH and nearly complete inhibition in the presence of 20/1000 (344 mM) ethanol. The IgE-induced degranulation of mBMMC cultured with EtOH for seven days was inhibited to a similar degree as the degranulation of mBMMC exposed to EtOH for only one hour. Inclusion of 5/1000 (86 mM) ethanol in the medium reduced tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 production in human mast cell line (HMC-1) cells by 55 +/- 7% and 19 +/- 5%, respectively, and the presence of 20/1000 (344 mM) ethanol inhibited the expression 81 +/- 12% and 59 +/- 14% respectively. These results suggest that, in contrast to previous assumption, ethanol inhibits several critical MC functions at least in vitro. This inhibition of mediator, and cytokine release in particular, could contribute to the immune deficiency associated with chronic alcohol consumption.
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PMID:Ethanol inhibits IgE-induced degranulation and cytokine production in cultured mouse and human mast cells. 1110 96

There is evidence that beta-amyloid (A beta) peptide infusion in vivo produces a degranulation of vascular mast cells. It would be useful to investigate the interaction between A beta and mast cells in a simple in vitro model system in order to determine the cellular mechanism by which exposure to A beta peptides results in mast cell degranulation. In the present study, the effect of A beta(1-42) upon the release of granular hexosaminidase and serotonin has been investigated using the cognate rat mast cell line, RBL-2H3. Sensitization of these cells for 1 h with anti-DNP IgE (monoclonal anti-dinitrophenyl) results in a large release of hexosaminidase and serotonin due to degranulation when the cells are exposed to DNP-HSA (albumin, human dinitrophenyl). Pretreatment overnight with A beta(1-42) (10 and 30 microM) did not affect either the basal or antigen-stimulated release of hexosaminidase or serotonin. A similar lack of effect of A beta(25-35) and the lipid peroxidation product HNE upon antigen-stimulated release of hexosaminidase or serotonin was also found. It is concluded that RBL-2H3 cells are not a useful model for mechanistic studies into the effects of beta-amyloid peptides upon vascular mast cells.
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PMID:Investigation into the effects of amyloid (1-42) beta-peptide upon basal and antigen-stimulated hexosaminidase and serotonin release from rat RBL-2H3 basophilic leukemia cells. 1129 5

A cell line, termed NCJ, was established from the bone marrow-derived mast cells (BMMCs) of NC/Nga mice that are mouse models for atopic dermatitis. NCJ cells expressed FcepsilonRI and c-kit and showed a metachromasia of the granules with a toluidine blue-positive and safranin-negative staining pattern that is characteristic for immature-type mast cells. Interestingly, NCJ cells showed proliferation independent of IL-3, which was associated with constitutive phosphorylation of Raf-1 and Erk kinases. Although NCJ cells had several characteristics of mast cells, we failed to detect FcepsilonRI-mediated beta-hexosaminidase release and its histamine content. These findings indicated that NCJ cells represented a mast cell line with an immature phenotype and the ability to proliferate in the absence of mast cell growth factors. NCJ cells might thus be useful to study the molecular basis of mast cell proliferation.
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PMID:Establishment and characterization of a murine mast cell line derived from NC/Nga mice. 1140 77

There are conflicting reports in the literature as to whether palmitoylethanolamide affects the function of mast cell-related cell lines in vitro, in contrast to the well-documented effects of this compound upon mast cell function in vivo. In the present study, we have reinvestigated the effects of palmitoylethanolamide upon antigen-induced release of [3H]serotonin and beta-hexosaminidase from rat basophilic leukemia RBL-2H3 cells and compared these effects with those of 2-arachidonoylglycerol, anandamide and R1-methanandamide. RBL-2H3 cells were sensitized with a monoclonal anti-DNP IgE, after which they were stimulated with antigen (DNP-HSA). Palmitoylethanolamide produced a small, but significant reduction in antigen-stimulated [3H]serotonin release at high concentrations, whereas anandamide was without effect. In contrast, 2-arachidonoylglycerol and methanandamide increased the antigen-stimulated release of both [3H]serotonin and beta-hexosaminidase. It is concluded that in RBL-2H3 cells, these cannabimimetic fatty acid derivatives do not have potent stabilizing effects upon antigen-induced degranulation.
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PMID:Effects of the cannabimimetic fatty acid derivatives 2-arachidonoylglycerol, anandamide, palmitoylethanolamide and methanandamide upon IgE-dependent antigen-induced beta-hexosaminidase, serotonin and TNF alpha release from rat RBL-2H3 basophilic leukaemic cells. 1148 41

Mast cells, essential effector cells in allergic inflammation, have been found to be activated in T cell-mediated inflammatory processes in accordance with their residence in close physical proximity to T cells. We have recently reported that mast cells release granule-associated mediators and TNF-alpha upon direct contact with activated T cells. This data suggested an unrecognized activation pathway, where mast cells may be activated during T cell-mediated inflammation. Herein, we show that this cell-cell contact results in the release of matrix metalloproteinase (MMP)-9 and the MMP inhibitor tissue inhibitor of metalloproteinase 1 from HMC-1 human mast cells or from mature peripheral blood-derived human mast cells. The expression and release of these mediators, as well as of beta-hexosaminidase and several cytokines, were also induced when mast cells were incubated with cell membranes isolated from activated, but not resting, T cells. Subcellular fractionation revealed that the mature form of MMP-9 cofractionated with histamine and tryptase, indicating its localization within the secretory granules. MMP-9 release was first detected at 6 h and peaked at 22 h of incubation with activated T cell membranes, while TNF-alpha release peaked after only 6 h. Anti-TNF-alpha mAb inhibited the T cell membrane-induced MMP-9 release, indicating a possible autocrine regulation of MMP release by mast cell TNF-alpha. This cascade of events, whereby mast cells are activated by T cells to release cytokines and MMP-9, which are known to be essential for leukocyte extravasation and recruitment to affected sites, points to an important immunoregulatory function of mast cells within the context of T cell-mediated inflammatory processes.
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PMID:Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha. 1156 20

Mast cells have been shown to produce endothelin-1 (ET-1) and to express ET receptors. Thus, we postulated that ETs modulate mast cell mediator production in an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with exogenous ET-1 or ET-3, and beta-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of beta-hexosaminidase and TNF and of mRNA expression. An antagonist of the ET(B) receptor subtype abrogated ET-stimulated TNF release, although ET(A) and ET(B) receptors have been identified by immunocytochemistry. It is interesting that ET-1 and ET-3 inhibited (25-30%) mRNA expression of Th2-type cytokines (IL-4, IL-10, and IL-13) and increased IL-12 release (39% and 41%, respectively) without affecting MIP-1alpha and NO production. Thus, our data suggest that ETs may play an important role in modulating the cytokine network by regulating Th1/Th2 cytokine production by mast cells.
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PMID:Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines. 1199 8

Because thrombin-induced inflammation is partially mast cell-dependent and involves proteinase-activated receptors (PARs), we hypothesized that mast cells express PAR and can be stimulated with PAR-activating peptides (PAR-AP). We demonstrated that rat peritoneal mast cells expressed PAR-1 and PAR-2 mRNA, and that PAR-2AP (tc-LIGRLO-NH(2), 1 microm) induced 64.2 +/- 4.4% specific beta-hexosaminidase release from peritoneal mast cells, whereas another PAR-2AP (SLIGRL-NH(2), 10 microM), trypsin (40 U/ml), and mast cell tryptase (1.5 microg/ml) did not. PAR-1AP (ApfFRChaCitY-NH(2), 10 microM) (Cit) induced 11.7 +/- 3.7% specific beta-hexosaminidase release, whereas another PAR-1AP (TFLLR-NH(2), 40 microM) and human thrombin (10 U/ml) did not. PAR-AP, tc-LIGRLO-NH(2), and Cit increased the free intracellular Ca(2+) concentration, whereas trypsin, tryptase, thrombin, and other PAR-APs did not. Desensitization of Ca(2+) flux with different agonists suggests that although tc-LIGRLO-NH(2), Cit, and compound 48/80 have similar mechanisms of action, tc-LIGRLO-NH(2) also activates mast cells by a mechanism distinct from that of 48/80. Using benzalkonium chloride, which antagonizes the actions of 48/80 by competing for the same G(i) protein, we determined that benzalkonium chloride suppressed tc-LIGRLO-NH(2)-mediated (0.1 microM) beta-hexosaminidase release by 62%. Moreover, removal of sialic acid from peritoneal mast cells, using neuraminidase (2 U/ml), inhibited Cit- (10 microM, 52%) and tc-LIGRLO-NH(2) (0.5 microM, 29%)-mediated beta-hexosaminidase release. Thus, tc-LIGRLO-NH(2) and Cit have at least partially similar mechanisms of action as 48/80. PAR-AP may therefore activate mast cells via multiple mechanisms that are distinct from those of classical PAR-1 and PAR-2. The responsiveness of mast cells to PAR-AP via a non-PAR-1/non-PAR-2 mechanism complicates the interpretation of in vivo studies using these peptides.
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PMID:Proteinase-activated receptor (PAR)-1 and -2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 and PAR-2. 1213 Jul 3

Asthma is a complex condition in which exposure to environmental antigens induces inflammatory reactions in the airway characterized by activation of mast cells and eosinophils. Mast cells are known to be the main effector cells in eliciting IgE-mediated allergic response. These cells secrete various substances that perpetuate inflammation and provoke airway smooth muscle (ASM) contraction. A newly recognized addition to the repertoire of FcepsilonRI-mediated signaling events is the activation of sphingosine kinase leading to the generation of the potent sphingolipid mediator, sphingosine-1-phosphate (S1P) from sphingosine. S1P secretion by the lung significantly increases after challenge with an allergen, adding this sphingolipid metabolite to the variety of mediators that are released during an allergic reaction [FASEB J. 15 (2001) 1212]. Indeed, similar to previous reports, we found that FcepsilonRI cross-linking not only increased cellular levels of S1P, it also markedly enhanced its secretion from rat basophilic leukemia RBL-2H3 cells. Moreover, S1P induced degranulation of RBL and bone marrow derived mast cells (BMMCs) cells as determined by hexosaminidase release. Treatment of BMMCs with the sphingosine kinase inhibitors, DL-threo-dihydrosphingosine and dimethylsphingosine, reduced IgE/Ag stimulated histamine release. RT-PCR analysis demonstrated that these mast cells express S1P receptors EDG-1 and EDG-5 but not EDG-3, EDG-6 or EDG-8 transcripts. Further studies are needed to determine whether IgE triggering results in transactivation of EDG-1 or EDG-5 present on mast cells and whether this is a critical event for mast cell activation.
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PMID:The roles of sphingosine-1-phosphate in asthma. 1221 90

Thrombin activates mast cells to release inflammatory mediators through a mechanism involving protease-activated receptor-1 (PAR-1). We hypothesized that PAR-1 activation would induce mast cell adhesion to fibronectin (FN). Fluorescent adhesion assay was performed in 96-well plates coated with FN (20 microg/ml). Murine bone marrow cultured mast cells (BMCMC) were used after 3-5 wk of culture (>98% mast cells by flow cytometry for c-Kit expression). Thrombin induced beta-hexosaminidase, IL-6, and matrix metalloproteinase-9 release from BMCMC. Thrombin and the PAR-1-activating peptide AparafluoroFRCyclohexylACitY-NH(2) (cit) induced BMCMC adhesion to FN in a dose-dependent fashion, while the PAR-1-inactive peptide FSLLRY-NH(2) had no effect. Thrombin and cit induced also BMCMC adhesion to laminin. Thrombin-mediated adhesion to FN was inhibited by anti-alpha(5) integrin Ab (51.1 +/- 6.7%; n = 5). The combination of anti-alpha(5) and anti-alpha(4) Abs induced higher inhibition (65.7 +/- 7.1%; n = 5). Unlike what is known for FcepsilonRI-mediated adhesion, PAR-1-mediated adhesion to FN did not increase mediator release. We then explored the signaling pathways involved in PAR-1-mediated mast cell adhesion. Thrombin and cit induced p44/42 and p38 phosphorylation. Pertussis toxin inhibited PAR-1-mediated BMCMC adhesion by 57.3 +/- 7.3% (n = 4), indicating that G(i) proteins are involved. Wortmannin and calphostin almost completely inhibited PAR-1-mediated mast cell adhesion, indicating that PI-3 kinase and protein kinase C are involved. Adhesion was partially inhibited by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 (24.5 +/- 3.3%; n = 3) and the p38 inhibitor SB203580 (25.1 +/- 10.4%; n = 3). The two inhibitors had additive effects. Therefore, thrombin mediates mast cell adhesion through the activation of G(i) proteins, phosphoinositol 3-kinase, protein kinase C, and mitogen-activated protein kinase pathways.
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PMID:Thrombin induces mast cell adhesion to fibronectin: evidence for involvement of protease-activated receptor-1. 1237 Mar 92

In the present study, the effects of systemic injection of radiographic contrast media (RCM) on vascular permeability was examined in various tissues of rats and the involvement of mast cell histamine in the RCM-induced vascular hyperpermeability subsequently determined. Both ionic (amidotrizoate) and non-ionic RCM (iohexol) enhanced vascular permeability specifically in lungs, as assessed by the extravasation of Evans blue (EB) dye. Another ionic RCM, ioxaglate, also markedly increased pulmonary vascular permeability and decreased pulmonary histamine content, whereby the extent of the reduction correlated well with the vascular hyperpermeability. Depletion of mast cells by prior treatment with compound 48/80 markedly attenuated the ioxaglate-induced enhancement of EB extravasation. The ioxaglate-increased extravasation was also inhibited by the mast cell stabilizer sodium cromoglicate and histamine H(1) and H(2) receptor antagonists. In isolated rat pulmonary mast cells, ioxaglate induced the concentration-dependent release of beta-hexosaminidase, an index of mast cell degranulation. The present findings thus show clearly that RCM causes the degradation of pulmonary mast cells and the resultant release of histamine that in turn increases vascular permeability by stimulating histamine H(1) and H(2) receptors.
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PMID:Evidence for involvement of mast cell degranulation and subsequent stimulation of histamine H1 and H2 receptors in radiographic contrast media-increased vascular permeability in rats. 1244 3


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