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 cross-linkage of high affinity Fc epsilon receptors (Fc epsilon RI) on mast cells and basophils is central to the induction of allergic inflammatory responses. As a result of such cross-linkage, mast cells secrete a variety of preformed biologically active substances, such as histamine, and newly synthesized arachidonic acid metabolites. Here we show that cross-linkage of Fc epsilon RI on a series of nontransformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2 cells). These factors include interleukin-3 (a mast cell growth factor)s interleukin-4 (an IgE 'switch factor'), interleukin-5 (an eosinophil differentiation factor) and interleukin-6 (a factor controlling immunoglobulin secretion). The production of these polypeptide factors by mast cells may have great importance in the induction of allergic and anti-parasite inflammatory responses.
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PMID:Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. 246 65

Based on homology with the mouse interleukin 4 (IL-4) cDNA that expresses B cell, T cell, and mast cell stimulating activities (Lee, F. et al., (1986) Proc. Natl. Acad. Sci. USA 83, 2061), we have isolated from a Balb/c mouse liver DNA library the mouse chromosomal gene and analyzed its overall structure. The gene occurs as a single copy in the haploid genome and contains four exons and three introns. The exon sequences almost completely match the cloned cDNA sequence. Interestingly, there is a fairly high degree of homology between mouse IL-4 and mouse IL-2 genes extending more than 200 bp upstream of a "TATA" like sequence located 20 bp upstream of the transcription initiation site. These sequences may play an important role in the regulated expression of this gene in concanavalin A or antigen-stimulated T lymphocytes. The supernatant of COS7 cells transfected with plasmid DNA containing the entire gene exhibited both T cell growth factor and mast cell growth factor activities.
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PMID:Structural analysis of the mouse chromosomal gene encoding interleukin 4 which expresses B cell, T cell and mast cell stimulating activities. 302 76

Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL-3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.
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PMID:Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. 326 64

BSF-1/interleukin-4, a product of activated T cells, has multiple biological activities that affect cells of most hematopoietic lineages. Among these is the ability of BSF-1 to costimulate the growth of mast cells and regulate the production of IgE. We demonstrate here that BSF-1 mRNA is expressed by a majority of transformed mast cell lines and by 5 IL-3-dependent non-transformed mast cell lines. BSF-1 activity, including the ability to enhance the growth of IL-3-dependent mast cells, was detected in the supernatants of transformed mast cells. The role of BSF-1 as a mast cell growth factor, its constitutive production by transformed mast cells, and the lack of IL-3 production by most of these cells raise the possibility that BSF-1 may act as an autocrine growth factor for some transformed mast cells. Furthermore, production of BSF-1 mRNA by nontransformed cells indicates that mast cells may be an important physiologic source of this factor.
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PMID:B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. 349 23

Bone marrow-derived cultured mast cells (BMMC) were transferred intravenously into W/WV mice to examine if they could reconstitute defective mucosal mast cell response or defective protective capacity against infection with Strongyloides ratti. When mast cell growth factor-producing activity of W/WV mice were examined, mesenteric lymph node cells obtained at 7 to 14 days after infection could produce this factor in vitro by stimulation with S. ratti-adult worm antigen. A single injection of BMMC (1 X 10(7] on day 7 post-infection (p.i.) neither caused an increase in number of intestinal mucosal mast cells not altered the kinetics of faecal larval output (LPG). On the other hand, serial injections of BMMC (5 X 10(6] from day 5 to 10 p.i. (total 3 X 10(7) cells) resulted in the significant increase in number of intestinal mucosal mast cells. However, this treatment too could not alter the kinetics of LPG. Therefore, adoptive transfer of BMMC could cause the increase in number of histologically detectable-mucosal mast cells, but these cells are, by themselves, not sufficient to cause the expulsion of S. ratti adult worms from the intestine.
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PMID:Reconstitution of mucosal mast cells in W/WV mice by adoptive transfer of bone marrow-derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti-infection. 356 59

Highly enriched preparations of intraepithelial lymphocytes (IEL) containing a large subpopulation of granulated cells were isolated from the murine small intestinal mucosa. We cultured IEL in media containing interleukin 2 (growth media conditioned with 20% concanavalin A supernatant; Con A CM) or mast cell growth factor(s) (growth media conditioned with 40% WEHI-3 supernatant; WEHI CM) and compared the physical and functional properties of the cultured cells to freshly isolated IEL. IEL cultured in Con A CM developed enhanced cytotoxicity against YAC-1, compared to freshly isolated IEL, and spontaneous cytotoxicity for P815 targets. Most of these cultured cells were Thy-1+ Lyt-1- Lyt-2+, and contained cytoplasmic granules similar to those seen in electron photomicrographs of other cytotoxic cell populations. IEL cultured in WEHI CM gave rise to cells that morphologically resembled mast cells. Unlike freshly isolated IEL, the cells stained metachromatically, contained 200-450 ng of histamine/10(6) cells and expressed high-affinity receptors for IgE. Our data clearly show that, although IEL do not themselves have physical characteristics of mast cells, they do contain mast cell precursors. In addition, IEL grown in the presence of T cell growth factors give rise to an activated cytotoxic cell population which is mostly granulated and Thy-1+ Lyt-1- Lyt-2+.
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PMID:Murine intestinal intraepithelial lymphocytes II. Comparison of freshly isolated and cultured intraepithelial lymphocytes. 392 52

Factors that stimulate the proliferation and differentiation of murine bone marrow cells have been purified from a cloned T cell lymphoma, LBRM-33, and a cloned myelomonocytic leukemia cell line, WEHI-3. These colony-stimulating factors (CSF) have been purified by sequential fractionation by using salt precipitation, gel filtration, anion and cation exchange chromatography, and high pressure liquid chromatography. Both LBRM-33 and WEHI-3 cells secrete a CSF species with similar chemical and biologic properties. This CSF species appears to exist in two forms, termed CSF-2 alpha and CSF-2 beta, both of which stimulate the growth of bone marrow cells in the granulocyte, macrophage, megakaryocyte, mast cell, and erythrocyte lineages, as well as the growth of a CSF-dependent cell line, FDC-P2. These properties of CSF-2 alpha and -2 beta are similar to those reported for interleukin 3, hematopoietic cell growth factor, mast cell growth factor, and persisting cell growth factor. However, LBRM-33 cells secrete another CSF species, not produced by WEHI-3 cells. This CSF species, unique to LBRM cells, is termed here CSF-2 gamma and it stimulates the proliferation of granulocytes and macrophages from bone marrow but does not support the growth of FDC-P2 cells.
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PMID:Biochemical comparison of murine colony-stimulating factors secreted by a T cell lymphoma and a myelomonocytic leukemia. 660 83

Activation of phosphatidylinositol (PI) 3-kinase is a common sequel to tyrosine kinase activation and appears to be essential for tyrosine kinases to induce proliferation. Since multiple hemopoietic growth factors activate tyrosine kinases, we investigated whether these growth factors activate PI 3-kinase. We show that interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), granulocyte-macrophage colony stimulating factor (GM-CSF), and steel factor (SLF) all activate PI 3-kinase. These cytokines increased the amount of PI 3-kinase activity that could be immunoprecipitated with anti-phosphotyrosine antibodies from the MC-9 mast cell line or from the hemopoietic progenitor cell line FDC-P1. Increases in this assay frequently correlate with PI 3-kinase activation in vivo. To determine directly whether these factors activate PI 3-kinase in vivo, we measured the levels of 3-phosphorylated inositol phospholipids in intact 32P-labeled MC-9 cells. IL-3, IL-4, IL-5, GM-CSF, and SLF all caused increased synthesis of the PI 3-kinase products phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with a relative potency of SLF >> IL-3 > IL-5, GM-CSF > IL-4. In contrast, IL-4 caused the largest increase in the in vitro anti-phosphotyrosine immune complex PI 3-kinase assay. Thus, the in vitro assay does not accurately reflect in vivo activation of PI 3-kinase. Cytokine treatment did not stimulate tyrosine phosphorylation of either the 85-kDa regulatory subunit or the 110-kDa catalytic subunit of PI 3-kinase and is therefore not required for activation of PI 3-kinase by these factors. Cytokine treatment did induce PI 3-kinase to associate with other tyrosine-phosphorylated proteins in a cytokine-specific manner. PI 3-kinase associated with c-kit after SLF stimulation, a 170-kDa protein after IL-4 stimulation, and a 70-kDa protein after treatment with IL-3 or GM-CSF. Thus, multiple hemopoietic growth factors that act through different types of receptors activate PI 3-kinase in vivo and induce factor-specific interactions of PI 3-kinase with other tyrosine-phosphorylated proteins.
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PMID:Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells. Association of the enzyme with various tyrosine-phosphorylated proteins. 750 38

Regulation of steel factor (SF) production in Sertoli cells from postnatal mouse testes was studied in a mast cell-Sertoli cell coculture system. Treatment of Sertoli cells with dibutyryl cAMP (50-1000 mumol l-1), forskolin (1-25 mmol l-1), and cholera toxin (10 micrograms ml-1) increased SF production, whereas FSH and theophylline had no significant effect. Furthermore, growth factors and testosterone, which would play some roles in spermatogenesis, were also tested, but none of these stimulated SF production. The constitutive production of SF may, rather, reflect the physiological condition of Sertoli cells in vivo.
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PMID:Effects of hormones, cyclic AMP analogues and growth factors on steel factor (SF) production in mouse Sertoli cell cultures. 750 77

Steel (SI) and white spotting (W) loci encode steel factor (c-kit ligand) and the c-kit tyrosine kinase receptor, respectively. Mutations at these loci affect migration and differentiation of primordial germ cells, neural crest-derived melanoblasts, and hematopoietic cells. In these processes, cell adhesion molecules are hypothesized to be crucial. We have examined the role of steel factor and c-kit in cell-extracellular matrix adhesion using bone marrow-derived mast cells as a model system. Steel factor stimulates mast cells to bind to fibronectin and, to a lesser extent, to vitronectin, whereas interleukin-3 and interleukin-4, which are also mast cell growth factors, do not. Activation of adhesiveness is transient, occurs at concentrations of steel factor 100-fold lower than required for growth stimulation, and requires the integrin VLA-5. Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase. By contrast, c-kit mutant and wild-type mast cells adhere equally well to COS cells expressing membrane-anchored steel factor, showing that the kinase activity of c-kit is not required for adhesion directly mediated by c-kit. Our findings suggest that regulation of adhesion is an important biologic function of steel factor.
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PMID:Steel factor and c-kit regulate cell-matrix adhesion. 750 7


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