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)

The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte-macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi-purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM-CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF.
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PMID:Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 288 59

The role of mast cells and mast-cell-derived factors in natural cytotoxic reactions was investigated. Cultured and freshly isolated murine mast cells are shown to be cytotoxic to WEHI-164 and YAC-1 targets in 18-hr viability assays but not in 4-hr assays. Here, we describe a cytotoxic factor in murine mast cells that is immunologically related to tumor necrosis factor (TNF). This TNF-like factor lyses WEHI-164 cells with a slow time course requiring 16-20 hr for the lytic reaction to complete. Antibodies specific for human and murine TNF and human lymphotoxin partially block mast cell lysis of WEHI-164 cells. These antibodies react on immunoblots with one major mast cell protein band of 50 kDa. Immunoblot analysis shows this factor in cloned and uncloned cultured mouse mast cells and in mature "connective tissue-type" mast cells freshly purified from rat or mouse peritoneal cavities. The amount of this factor is greatly enhanced in cells that have been stimulated with a combination of phorbol ester/concanavalin A or bacterial lipopolysaccharide. Subcellular fractionation analysis of mast cells with Percoll gradients reveals two pools of TNF-related cytotoxic activity that are associated with free cytosolic material and granule fractions. In contrast to cytotoxic T lymphocytes and natural killer cells, granule-enriched fractions of mast cells do not contain any hemolytic activity. The localization of the TNF-like molecule in mast cell granules may play a strategical role in the rapid delivery of this mediator to the target cell membrane following cell surface stimulation and degranulation.
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PMID:Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. 332 Oct 69

The capacity of mast cell products to mediate T-cell adhesion to fibroblasts was explored using heterotypic coculture systems or by exposing fibroblasts to mast-cell-conditioned media (MCCM), prepared by degranulating mast cells with calcium ionophore. Experimental results indicated that fibroblasts exposed to MCCM for 24 h bound fivefold more T cells than control fibroblasts. Binding was inhibited with intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1) neutralizing antibodies. Enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis revealed that fibroblasts exposed to MCCM markedly increased ICAM-1 and VCAM-1 surface expression by 4 h, with levels maximal at 16 h and returning toward baseline by 48 h. A dose-dependent response of ICAM-1 and VCAM-1 expression was noted using serial dilutions of MCCM or by altering the ratio of degranulated mast cells cocultured with fibroblasts. Similar results were obtained using human fibroblasts derived from the dermis, synovium, and lung, although lung fibroblasts were generally less responsive. Northern analysis confirmed that MCCM regulated ICAM-1 and VCAM-1 expression at the mRNA level. In summary, mast cell products stimulated fibroblast surface expression, steady-state mRNA levels, and functional expression of ICAM-1 and VCAM-1. Experimental data suggest that mast-cell-derived tumor necrosis factor-alpha may be in large part responsible for these observations, although further studies using human mast cells will be required. Using a skin-equivalent organotypic coculture model with fibroblasts admixed with mast cells, we observed increased ICAM-1 expression in both keratinocytes and fibroblasts after activation of the mast cells.
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PMID:Mast cells induce T-cell adhesion to human fibroblasts by regulating intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. 749 Apr 73

To obtain further information regarding the role of cytokines during mast cell differentiation, we have investigated changes of cytokine secretion in mast cells developing from the human peripheral blood monocytic cell fraction during culture with fibroblast-derived conditioned media. The influence of stem cell factor and an antibody to the respective receptor in our culture system was studied as well. Interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)alpha were spontaneously secreted by cultured cells at day 1 and decreased markedly by day 14. Similar changes occurred also during culture with stem cell factor and were partially abrogated by an anti-receptor antibody. IL-8 was secreted at a high level throughout the culture, whereas no spontaneous secretion of IL-2, IL-3, IL-4, and IL-7 was measured at all. Upon stimulation with phorbol myristate acetate and A23187, cultured cells showed substantially more release of IL-3 and TNF-alpha after 14 d of culture, compared to peripheral blood monocytic cells. Preformed TNF-alpha was found in one of three monocytic cell preparations from peripheral blood, but not in monocytic cell-derived mast cells. During mast cell differentiation, cytokines from monocytic cells are therefore downregulated while the cells assume a pattern typically found in mast cells.
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PMID:Comparative cytokine release from human monocytes, monocyte-derived immature mast cells, and a human mast cell line (HMC-1). 752 30

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell-shaped dose-response curve. Another potent angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase-inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.
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PMID:Angiogenic factors stimulate mast-cell migration. 754 57

To investigate the modulated proliferation of an interleukin-3(IL-3)-dependent cell by exogenous ganglioside GM3, mouse bone marrow-derived mast cells (BMMC) were cultured with various concentrations of GM3 in the presence of IL-3. By 4 weeks of culture, most of the nonadherent cells were alcian blue-positive mast cells. Culturing 2-week-cultured BMMC with GM3 for 1 week reduced the number of alcian blue-positive cells, but the increased total histamine content of BMMC was observed. To examine the effect of GM3 on the synergistic response by IL-3 and interleukin-4 (IL-4), 3-week-cultured BMMC were cultured with GM3 in the presence of IL-3 and IL-4 for 1 week. Although the addition of IL-4 to culture medium increased the number of BMMC, treatment with GM3 reduced its proliferative activity. Concerning the effect of GM3 on cell membrane, there are no changes in the expression of IgE receptors on BMMC treated with GM3 though a low concentration of GM3 increased it. However, the production of tumor necrosis factor-alpha from BMMC treated with GM3 was significantly suppressed. These results indicate that in vitro treatment with exogenous GM3 inhibited the proliferative response of IL-3-dependent mast cell populations and modulated its characteristics.
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PMID:Ganglioside GM3 inhibits interleukin-3-dependent bone marrow-derived mast cell proliferation. 762 Mar 68

The expression of surface procoagulants by macrophages represents an important mechanism underlying local fibrin deposition at sites of extravascular inflammation. Mast cells by virtue of their perivascular location are in a potent position to influence the inflammatory process. The present studies investigated the role of the mast cell in the generation of macrophage procoagulant activity (PCA) and tumor necrosis factor (TNF) production. Mast cell lysates caused a marked induction of macrophage PCA (dose and time dependent) and TNF release while whole mast cells had little effect. This effect was prevented by the tyrosine kinase inhibitor herbimycin. At the molecular level, Northern blot analysis revealed marked induction of the murine macrophage tissue factor transcript in response to incubation with mast cell lysate compared to control. These studies thus suggest that mast cell-macrophage interactions promote macrophage-mediated fibrin deposition and TNF release and that this effect is in part mediated via induction of tyrosine phosphorylation. These observations suggest novel mechanisms of involvement of the mast cell in the inflammatory microenvironment and macrophage activation.
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PMID:Mast cell modulation of macrophage procoagulant activity and TNF production. 763 Jan 10

Myelin basic protein (MBP)-specific SJL/J T cells were cultured in normal growth medium or growth medium supplemented with 10% culture supernatant from WEHI-3 cells, a source of interleukin-3 (IL-3), or with recombinant IL-3. T cell lines cultured with IL-3 supplementation were more encephalitogenic compared to parallel lines cultured without this supplement. There was little difference in antigen-specific proliferative response or expression of cell surface markers CD3, CD4, CD8, IL-2R, or alpha/beta TCR in the parallel lines. Supernatant fluids from antigen-stimulated T cells from each cycle were tested for the presence of IL-2, IL-3, IL-4, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha/beta) and transforming growth factor-beta (TGF beta). No significant difference in IL-2, IL-4, GM-CSF, TNF alpha/beta, or TGF beta levels were seen when supplemented and unsupplemented cultures were compared. Supernatant culture fluids contained an activity that was highly stimulatory for the IL-3-dependent mouse mast cell line, MC/9. This activity was attributable to a combination of at least three factors that varied in relative concentrations throughout the course of the experiments. Based on neutralization by monoclonal antibodies, MC/9 stimulating activity in early passage lines was attributable entirely to IL-3 and GM-CSF. The fraction of the MC/9 stimulatory activity that could be neutralized by monoclonal antibody to IL-3 decreased with increasing stimulation cycle while the fraction neutralized by anti-GM-CSF antibodies remained relatively constant. At the time that the lines lost encephalitogenicity, the activity neutralizable by anti-IL-3 had dropped to low levels in the culture supernatants; however, MC/9 stimulatory activity remained present in the supernatants. This was due to GM-CSF and a third unidentified factor.
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PMID:Interleukin-3 and encephalitogenic activity of SJL/J myelin basic protein-specific T cell lines. 768 50

To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitrite-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitrite or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-alpha-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-alpha-dependent cytotoxicity. However, low concentrations of nitrite (< 1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions.
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PMID:Further studies on the effect of nitrogen dioxide on mast cells: the effect of the metabolite, nitrite. 768 33

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells modulate allergic pulmonary eosinophilia in mice. 769 19


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