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

We studied MHC class II gene expression and its regulation by IFN-gamma in purified rat peritoneal connective tissue-type mast cells. Mast cells were cultured with or without recombinant rat IFN-gamma (70 ng/ml) for 48 hr and analyzed by RT-PCR for expression of mRNA encoding MHC class II and by fluorescence flow cytometry for surface expression of MHC class II protein product. Levels of MHC class II mRNA and cell-surface protein product in untreated mast cells remained constant throughout the culture period but increased progressively after treatment with IFN-gamma such that by 48 hr levels were significantly greater than those in untreated cells. Dual labeling confirmed that MHC class II product was coexpressed with IgE (a mast cell marker). To conclude, rat connective tissue-type mast cells express mRNA and surface product for the MHC class II gene which can be up-regulated by IFN-gamma.
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PMID:Rat connective tissue-type mast cells express MHC class II: up-regulation by IFN-gamma. 760 95

We recently showed that bone marrow-derived mast cells bore MHC class II molecules and could present antigens to specific T cell hybridomas. This article summarizes the effects of purified recombinant cytokines on the expression of MHC class II molecules by mast cells and on their antigen-presenting capacity. Since IL-3 is essential for mast cell growth, all the cytokines were analyzed in the presence of IL-3. IL-3 downregulated the production of Ia molecules, so that mast cells cultured in IL-3 alone had no antigen presenting ability. In contrast, IL-4 and IFN-gamma upregulated the production of MHC class II molecules, while GM-CSF had no effect. The antigen-presenting capacity of IL-4-treated mast cells was substantially enhanced by incubating these cells with GM-CSF for 2 days. GM-CSF enhanced antigen presentation only in combination with IL-4. The activation of mast cells was reversible and could not be repeated. Finally, incubation of IL-4- or IL-4/GM-CSF-treated mast cells with IFN-gamma led to almost complete inhibition of the antigen-presenting function. These findings provide new insights into the regulation of specific allergic responses.
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PMID:Presentation of soluble antigens by mast cells: upregulation by interleukin-4 and granulocyte/macrophage colony-stimulating factor and downregulation by interferon-gamma. 775 29

Rat peritoneal mast cells were examined to determine whether mast cells can stimulate T cell proliferation through antigen presentation. Mast cells were obtained by peritoneal lavage and purified to 98% using density gradient centrifugation. Purified peritoneal mast cells expressed MHC class II molecules as determined by flow cytometry using monoclonal antibody OX6 specific for common determinants of rat class II. The intensity of class II expression by mast cells was not significantly increased upon incubation with recombinant rat IFN-gamma. Peritoneal mast cells also were found to express the accessory molecules ICAM-1 (CD54) and LFA-1 beta (CD18) but not LFA-1 alpha (CD11a). In the presence of antigen, purified mast cells stimulated proliferation of an autologous CD4+, PPD-specific T cell line. This stimulation was blocked by OX6 antibody, confirming that the proliferation was class II dependent. T cell proliferation was similarly induced by purified mast cell populations that were completely monocyte and macrophages depleted. These results demonstrate that mast cells, through their expression of MHC class II and accessory molecules, are capable of antigen presentation.
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PMID:Rat peritoneal mast cells present antigen to a PPD-specific T cell line. 791 67

This paper describes a new role for mast cells as being able to present Ag to immune T cells. A mouse bone marrow-derived mast cell population obtained after 3 wk of culture in a conditioned medium has been shown to express a variety of membrane-associated Ag, including MHC class II and class I Ag, CD23, CD32, high affinity receptor for IgE, and CD4. Expression of MHC class II molecules was up-regulated upon stimulation with LPS but not with IFN-gamma and was down-regulated after exposure of mast cells to IL-3 treatment. We have demonstrated that mast cells were able to present native Ag as well as immunogenic peptides to MHC class II-restricted T cell hybridoma. The inhibition of Ag presentation after mast cells have been treated with ammonia suggests that Ag catabolism in intracytoplasmic compartment as a key step in Ag handling takes place in these cells. The MHC class II molecule is the restricting element for the presentation of OVA and the lambda repressor from bacteriophage lambda to a panel of specific T cell hybridomas, as demonstrated by the blocking effect of anti-MHC class II mAb on the Ag-presenting function. A characteristic feature of mast cells is the generation of a narrower immunogenic peptide repertoire as compared with A20 and LBB 3.4.16, a B lymphoma cell line, and a B cell hybridoma, respectively. This novel function of mast cells brings to a much closer connection inflammatory and immunologic processes and sheds new light on the biology of mast cells and particularly on the specific allergic responses.
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PMID:Antigen-dependent stimulation by bone marrow-derived mast cells of MHC class II-restricted T cell hybridoma. 824 70

We have examined the effects of mercuric chloride (HgCl2) on growth and IL-4, IL-8, TNF-alpha and MHC class II gene expression in the HMC-1 human leukemic mast cell line. Proliferation, measured by [3H]thymidine incorporation or production of a formazan product (MTT assay), was substantially inhibited by HgCl2 at concentrations of 10(-6) M and above. Inspection of the DNA by agarose gel electrophoresis from HgCl2-treated cells revealed that it was intact, indicating inhibition of DNA synthesis, but not denaturation. HgCl2 inhibited expression of mRNA for IL-8, TNF-alpha and MHC class II at 4 x 10(-6) M and inhibited expression of IL-4 mRNA at 8 x 10(-6) M and above. At a concentration of 10(-5)M, HgCl2 almost completely blocked mRNA expression for IL-4, IL-8, TNF-alpha and MHC class II, but produced negligible inhibition of expression of mRNA encoding the housekeeping gene beta-actin, thus demonstrating selective toxicity for the cytokine and MHC class II genes studied. Pre-exposure of the cells to human recombinant IL-4 prior to treatment with HgCl2 had no effect on expression levels of any of the genes examined. The effects seen in this study are consistent with previous reports showing immunotoxic effects of HgCl2 on other cell types, therefore, the HMC-1 mast cell line may prove useful in further studies of mast cell cytokine gene expression and the mechanisms involved in cytokine gene toxicity.
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PMID:The effects of mercuric chloride on growth, cytokine and MHC class II gene expression in a human leukemic mast cell line. 856 Apr 97

The expression of MHC class II molecules by human mast cells has been reported in immunohistochemical surveys of inflammatory conditions, such as in tuberculin hypersensitivity. While these data suggest that human mast cells may act as antigen-presenting cells under inflammatory conditions, the induction of class II antigens on human mast cells has not been examined. In this study, we determined the effects of the inflammatory cytokines IFN-gamma and IL-4 on the expression of class II antigens HLA-DR, -DP, and -DQ by the human mast cell line HMC-1. HMC-1 cells were incubated with or without 1000 U/ml recombinant human IFN-gamma (rhIFN-gamma) and IL-4 (rhIL-4) for 72 hr and analyzed for expression of MHC class II antigens by direct immunofluorescence and flow cytometry. HMC-1 cells expressed significant levels of HLA-DR and moderate levels of HLA-DP and -DQ at baseline and when cultured without exogenous cytokines. Stimulation by rhIFN-gamma for 72 hr significantly increased the levels of HLA-DR and -DP expression but did not affect levels of HLA-DQ. Stimulation by rhIL-4 for 72 hr had minimal effect on expression of class II molecules, but induced a significant difference in levels of ICAM-1 (CD54) expression, indicating that this cytokine is involved instead in the control of certain accessory molecules. Our data showing constitutive expression of MHC class II molecules on HMC-1 cells and upregulation of that expression by rhIFN-gamma suggest that human mast cells function as antigen-presenting cells at sites where inflammatory cytokines are present.
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PMID:IFN-gamma-stimulated enhancement of MHC class II antigen expression by the human mast cell line HMC-1. 866 Aug 3

Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.
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PMID:Rat peritoneal mast cells produce IFN-gamma following IL-12 treatment but not in response to IgE-mediated activation. 875 36

IFN-gamma regulates various aspects of rodent peritoneal mast cell function, including mediator release, cell growth, TNF-alpha-mediated cytotoxicity, and MHC class II expression. We investigated whether the suppressive action of IFN-gamma on IgE/Ag-mediated degranulation of mast cells is mediated via synthesis of nitric oxide. Incubation of mouse peritoneal cells with L-NMMA, an inhibitor of nitric oxide synthase, or in medium lacking the nitric oxide precursor L-arginine reversed the inhibitory effect of IFN-gamma on Ag-induced serotonin release. Furthermore, the nitric oxide donors sodium nitroprusside and S-nitrosoglutathione inhibited degranulation, and this effect was direct, since it was seen equally on purified and unfractionated mast cells and occurred independently of IFN-gammaR expression. Additional experiments revealed that accessory cells in peritoneal cell populations were the principal target for the action of IFN-gamma and the main source of nitric oxide; the cytokine was more potent on unfractionated compared with purified mast cells, and IFN-gamma induced detectable nitrite production in mixed peritoneal cells, but not in purified mast cells. These studies show that IFN-gamma induces nitric oxide production in peritoneal cell populations, and that synthesized nitric oxide directly inhibits the IgE-mediated secretory function of mast cells. The activation of nitric oxide-producing cells in the tissue microenvironment may be important in the control of mast cell-dependent allergic reactions.
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PMID:Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis. 923 42

To investigate the relationship between major histocompatibility complex (MHC) class II compartments, secretory granules, and secretory lysosomes, we analyzed the localization and fate of MHC class II molecules in mast cells. In bone marrow-derived mast cells, the bulk of MHC class II molecules is contained in two distinct compartments, with features of both lysosomal compartments and secretory granules defined by their protein content and their accessibility to endocytic tracers. Type I granules display internal membrane vesicles and are accessed by exogenous molecules after a time lag of 20 min; type II granules are reached by the endocytic tracer later and possess a serotonin-rich electron-dense core surrounded by a multivesicular domain. In these type I and type II granules, MHC class II molecules, mannose-6-phosphate receptors and lysosomal membrane proteins (lamp1 and lamp2) localize to small intralumenal vesicles. These 60-80-nm vesicles are released along with inflammatory mediators during mast cell degranulation triggered by IgE-antigen complexes. These observations emphasize the intimate connection between the endocytic and secretory pathways in cells of the hematopoietic lineage which allows regulated secretion of the contents of secretory lysosomes, including membrane proteins associated with small vesicles.
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PMID:Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. 939 81

We have previously shown that mouse bone marrow-derived mast cells (BMMC) can process and present immunogenic peptides to CD4 T cells. Here, we report on a T cell-dependent MHC class II-mediated mast cell activation resulting in IL-4 transcription and protein release. Presentation of optimal doses of ovalbumin peptide 323-339 resulted in IL-2 production by a specific T cell hybridoma and increase in IL-4 mRNA transcription in mast cells. IL-4 mRNA transcription increased by 200-fold in mast cells treated in IL-3/IL-4/granulocyte-macrophage colony-stimulating factor (high presenters) whereas only a tenfold increase or no increase were obtained with IL-3/IL-4/IFN-gamma- or IL-3-treated mast cells (low presenters), respectively. Induction of IL-4 mRNA transcription in purified mast cells by direct ligation of MHC class II molecules, using anti-I-A and anti-I-E-coated beads, indicates that MHC class II molecules are critical in this signaling pathway. However, when compared to T cells, anti-MHC class II-coated beads were less efficient, indicating a potential role of accessory molecules in this mast cell activation process. IgE-independent IL-4 production by mast cells as a result of cognate interaction with CD4 T cells could be critical for the development of type 2 responses. This novel mechanism may contribute to the induction and/or amplification of specific IgE-mediated allergic responses.
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PMID:IL-4 mRNA transcription is induced in mouse bone marrow-derived mast cells through an MHC class II-dependent signaling pathway. 954 79


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