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)

Murine interleukin 3 (IL-3) induces a strong, concomitant increase in histamine, interleukin 6 (IL-6), and interleukin 4 (IL-4) synthesis by progenitor-enriched bone marrow cell populations, whereas interleukin 2 (IL-2) or interferon-gamma (IFN-gamma) are undetectable. This phenomenon is observed between 4 and 12 h after exposure to the growth factor and attains maximal cytokine and histamine levels within 24 and 48 h, respectively. None of these mediators is produced by lymphoid populations such as lymph node cells or by granulocytes. Splenocytes secrete only low histamine and IL-6 levels, in accordance with the lower incidence of progenitors in the spleen, whereas total bone marrow cells generate substantial amounts of the three mediators even before enrichment. Histamine, IL-4-, and IL-6-producing cells copurify with immature cells and cannot be separated from each other throughout the sorting procedures used herein. They are concentrated in the low-density layers (buoyant density 1.069-1.086 g/cm3) of a discontinuous Ficoll gradient (less than 4% of the total bone marrow) together with the majority of hematopoietic progenitors (marrow-repopulating ability [MRA] cells, spleen colony-forming units [CFU-S] day-8 and day-12, granulocyte-macrophage colony-forming units [CFU-GM], and mast cell precursors). Their lightscatter characteristics are those of relatively large, granular cells. They do not belong to the most primitive stem cell subset (MRA and part of CFU-S day-12), but to a population with high mitochondrial activity identified by their important rhodamine retention (colony-forming unit cells [CFU-C], blast cells). In addition, we provide evidence that histamine, IL-4, and IL-6 do not depend on each other for their respective expression. Taken together, our data are consistent with the notion that in certain conditions, immature hematopoietic cells are a potent source of histamine and cytokines.
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PMID:Concomitant histamine, interleukin 4, and interleukin 6 production by hematopoietic progenitor subsets in response to interleukin 3. 183 45

Cultured mast cells derived from murine bone marrow were investigated for the presence of specific interferon-gamma (IFN-gamma) receptors, and for the effects of IFN-gamma on mast cell proliferation. 125I-labeled recombinant IFN-gamma (125I-Mu-rIFN-gamma) was shown to bind to high-affinity receptors on these cells. Scatchard analysis of binding data indicated the presence of about 500 homogeneous binding sites per cell, with an apparent equilibrium dissociation constant of 3 X 10(-10) M. The binding of 125I-Mu-rIFN-gamma to mast cells was inhibited by unlabeled Mu-rIFN-gamma but not by unlabeled Mu-IFN-alpha/beta. Cross-linking of 125I-Mu-rIFN-gamma to mast cell membrane proteins using a cross-linking agent yielded a predominant complex of 100 +/- 10 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography which most likely represents the IFN-gamma-receptor complex. To assess the biological significance of these receptors, we studied the effects of Mu-rIFN-gamma on mast cell proliferation, which was markedly inhibited in mast cell precursors but not in mature mast cells. These in vitro results are in agreement with the antiproliferative effect of IFN-gamma previously reported for other hematopoietic progenitors, and suggest that IFN-gamma could find its application in the treatment of human systemic mastocytosis.
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PMID:Specific high-affinity receptors for interferon-gamma on mouse bone marrow-derived mast cells: inhibitory effect of interferon-gamma on mast cell precursors. 213 79

Current studies on IgE-dependent allergic reactions focus on the regulation of IgE synthesis by cellular IgE receptors or by their fragments, so-called IgE-binding factors. Recent studies suggest that lymphokines, such as interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), may be more relevant in the modulation of IgE synthesis. Under this aspect studies should concentrate on the role of anti-isotypical anti-IgE antibodies which can be found frequently in IgE-mediated responses. Further studies have given new insights in the variation of releasability and lymphokine-mediated conditioning of effector cells, depending on the type of allergic reaction. Pretreatment of neutrophils with granulocyte macrophage- colony stimulating factor (GM-CSF), or basophils with interleukin-3 (IL-3) renders these cells capable of producing or releasing inflammatory mediators, such as histamine, leukotrienes or platelet activating-factor (PAF). The fact that the interaction of purified lymphokines, such as IL-3 or IL-8 with basophils causes the release of mediators, indicates a possible mechanism for the induction of immediate and delayed allergic reactions. New insights in these mechanisms may offer new immunopharmacological aspects in the treatment of allergic reactions. IgE-mediated allergic reactions can be divided into two distinct phases. During the period of sensitization allergen exposure causes the production of class E immunoglobulins (IgE) in genetically predisposed persons. Repeated allergen exposure in sensitized persons leads to bridging of IgE molecules with basophils or mast cell membranes which finally causes the production and the release of inflammation mediators, such as histamine, leukotrienes and PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New perspectives in the modulation of allergic inflammation]. 213 73

We report a case of a patient with systemic mastocytosis who was treated with interferon-gamma. Because of severe diarrhoea, nausea and weight loss due to mast cell infiltration of the gastric mucosa the patient received 150 micrograms d-1 interferon-gamma subcutaneously for 10 months. During therapy, the plasma concentrations of IL-3, IL-4 and GM-CSF, which seem to play a role in mast cell growth and differentiation were monitored. The patient had good symptomatic relief and the initially very high eosinophil counts in the peripheral blood showed a partial reduction. However, after 4 months of therapy the patient relapsed. In serum obtained after the relapse, but not in stored serum from the beginning of the therapy, neutralizing antibodies against interferon-gamma were found. Therefore an initial response to the therapy and a secondary failure mediated by treatment-induced antibodies against recombinant interferon-gamma might be suggested. Interferon-gamma may be a well tolerated therapeutic option in systemic mastocytosis. However, treatment-induced neutralizing antibodies against recombinant interferon-gamma should be considered if secondary treatment failure occurs.
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PMID:Treatment of systemic mastocytosis with interferon-gamma: failure after appearance of anti-IFN-gamma antibodies. 758 19

Allergen injection immunotherapy in selected patients is effective and has wide ranging anti-inflammatory effects. These include modulation of serum (and presumably local) IgE and IgG antibody responses, a reduction in mast cell numbers in the target organ and inhibition of mast cell mediator release. Tissue eosinophilia and eosinophil activation are also reduced. We have compared and contrasted the effects of immunotherapy and topical corticosteroids on allergen-induced late nasal responses. Both treatments inhibit allergen-induced late nasal symptoms and associated CD4+ T cell and eosinophil recruitment, possibly by distinct mechanisms. Whereas topical corticosteroids may act by suppressing cytokine mRNA expression for Th2-type cytokines, particularly interleukin-4, immunotherapy induces a local Th1 response with an increase in interferon-gamma.
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PMID:Changes in allergic inflammation associated with successful immunotherapy. 761 51

Interleukin 12 (IL-12: natural killer cell stimulatory factor, NKSF; cytotoxic lymphocyte maturation factor, CLMF) was studied for its effect on colony formation and lineage expression of low-density bone marrow cells from 5-fluorouracil-treated mice, and of sorted stem cells using a semi-solid culture assay in the absence or presence of IL-3, IL-11, Steel factor (SF) and erythropoietin. IL-12 did not support colony formation as a single factor, nor in the presence of IL-11 or SF. In IL-3-containing cultures, IL-12 slightly enhanced neutrophilic and monocyte differentiation. Both SF and IL-11 synergized with IL-3 to increase the percentage of multilineage colonies and the number of colonies containing erythrocytes, megakaryocytes, neutrophils, eosinophils, monocytes/macrophages, and blast cells, but not mast cells. In the presence of IL-3 + IL-11, IL-12 greatly enhanced neutrophil, megakaryocyte, erythrocyte, and mast cell development. In IL-3 + SF-containing cultures, IL-12 further increased colony numbers and a higher percentage of colonies expressed neutrophilic, megakaryocytic, erythroid, monocytic, blast cell, and/or mast cell lineages. Colony size and the presence of eosinophils in colonies were unaffected by IL-12 addition. These effects of IL-12 could not be reversed by antibodies against interferon-gamma. Our data show that IL-12 may act as a synergistic factor, stimulating multilineage expression of hemopoietic stem cells, probably via a direct action. The observed activity of IL-12, however, required the presence of a least two factors, i.e. either IL-3 + IL-11, or IL-3 + SF.
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PMID:Interleukin-12 enhances interleukin-3 dependent multilineage hematopoietic colony formation stimulated by interleukin-11 or steel factor. 769 Apr 39

In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T-cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor-beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory role in the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic subjects still remain obscure. Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells.
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PMID:Regulation of the development of type 2 T-helper cells in allergy. 771 Jul 7

The role of mast cells in provoking immediate-type hypersensitivity reactions is well established, but their involvement in chronic inflammation and immune reactions is not so clear. Mast cells synthesize and secrete large amounts of active proteinases, including tryptase, chymase, carboxypeptidase and cathepsin G, which can rapidly process numerous biologically active peptides and proteins or their precursors. Furthermore, mast cells are able to produce a variety of cytokines such as interleukin-4 (IL-4), IL-5, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) which are known to be intensively involved in modulating and directing inflammatory responses in the skin. In this review, the role of mast cell proteinases and cytokines in skin inflammation is discussed.
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PMID:Mast cell proteinases and cytokines in skin inflammation. 772 38

Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood (PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
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PMID:Expression of a mast cell tryptase in the human monocytic cell lines U-937 and Mono Mac 6. 821 Sep 98

Immunohistology and in situ hybridization were used to evaluate the presence, activation status, and cytokine mRNA profile of cells in the bronchial mucosa during human allergen-induced asthma. Fifteen atopic asthmatic subjects underwent inhalation challenge with allergen and with allergen diluent, performed in random order separated by an interval of at least 3 wk. Bronchial biopsies were obtained 24 h after challenge. Immunostaining revealed increases in the numbers of secreting eosinophils (EG2+; P < 0.05) and in interleukin-2 receptor (IL-2R)-positive cells (CD25+; P < 0.01) after allergen compared with diluent challenge. No differences were observed in the numbers of total leukocytes (CD45+), T lymphocytes (CD3+, CD4+, and CD8+), elastase-positive neutrophils, macrophages (CD68+), or mast cell subtypes (MCT+ or MCTC+). In situ hybridization revealed significant increases in the numbers of cells expressing mRNA for IL-5 (P < 0.02) and granulocyte/macrophage colony-stimulating factor (P < 0.01) after allergen compared with diluent challenge. A significant inverse relationship was observed between the number of cells expressing mRNA for IL-4 and for interferon-gamma (r = -0.75, P < 0.02). The results support the view that cytokines possibly from activated T lymphocytes may contribute to local eosinophil accumulation during allergen-induced asthma.
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PMID:Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. 841 55


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