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 9 (mIL-9) is a novel T-cell-derived lymphokine previously described as a T-cell growth factor (P40/TCGFIII) and as a mast cell growth-enhancing activity (MEA). In the present study we examined the potency of recombinant (r)mIL-9 to exhibit hemopoietic growth factor activity in the human system. In semisolid cultures of normal human bone marrow-derived mononuclear cells, rmIL-9 alone at a concentration range from 25 to 200 U/ml did not reveal any colony-stimulating activity on human granulocyte-macrophage colony-forming cells (GM-CFC), erythroid colony-forming units (CFU-E), and erythroid burst-forming units (BFU-E). Furthermore, we did not observe synergistic effects of rmIL-9 on the number, size, and morphological composition of human granulocyte-macrophage colonies in cultures stimulated with giant cell tumor-conditioned medium. However, a synergistic effect of rmIL-9 in the human erythropoietic culture system was clearly demonstrated in the presence of recombinant human erythropoietin (rhEpo). Recombinant murine IL-9 at a concentration of 200 U/ml enhanced the number of BFU-E-derived day-14 colonies about 3.6-fold as compared to control cultures stimulated with Epo alone. The formation of CFU-E-derived day-7 colonies was not significantly altered under the same conditions. Our results demonstrate that in the presence of rhEpo, rmIL-9 is synergistically active in human bone marrow cultures as an erythroid burst-promoting factor. The development of granulocyte-macrophage colonies obviously is not affected. This finding strongly suggests that mIL-9 can mediate signals via human IL-9 receptors and further extends the range of biological activities hitherto ascribed to mIL-9.
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PMID:Recombinant murine interleukin 9 enhances the erythropoietin-dependent colony formation of human BFU-E. 158 1

Mouse bone marrow hematopoietic stem cells were isolated from mouse femur bone and cultured in RPMI 1640 supplemented medium with 20 units/ml of the purified T-cell lymphokine, interleukin 3 (IL-3), IL-3 was uniquely able to induce the proliferation and differentiation of mature mast cells in vitro. The sparse granulation of the bone marrow-derived mast cells (BMMC) can be seen by day 5, progressing to definable mast cells by day 7, the mast cells appear morphologically mature and comprise a 96% pure population after 14 days of the culture. The monocytes macrophages, eosinophils and neutrophils disappeared by day 9. After 4 weeks of tissue culture, mast cells are fully mature and completely granulated at 98% cell purity. The BMMC are mononuclear, oval or round in shape and appear smaller than rat peritoneal mast cells. BMMC are stable over 3-5 months in conditioned medium. The homogeneous mast cell population possesses membrane receptors and mediators, such as histamine in their metachromatic granules. The histamine content of BMMC in culture between 2 to 4 weeks rose from 1.43 to 1.82 pg/cell. Moreover, the percentage of histamine release caused by 0.1 microM and 1.0 microM ionophore A23187 was 15% and 35%, respectively. By contrast, the histamine releasing activity of 0.01% and 0.001% compound 48/80 were 12 +/- 2% and 59 +/- 7% respectively. The granular density, histamine content and histamine release activity of BMMC are different from that of peritoneal mast cells.
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PMID:Effect of interleukin 3 on the differentiation and histamine content of cultured bone marrow mast cells. 170 84

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
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PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

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

IL-3, a pleiotropic lymphokine, has been termed mast cell growth factor because it promotes growth and differentiation of murine mast cells. Murine mast cells, in turn, express cell surface receptors for IL-3. Human rIL-3 has been shown to induce proliferation and differentiation of human basophils and to activate basophils via high affinity binding sites. To investigate whether human mast cells express IL-3R, binding studies with 125I-radiolabeled human rIL-3 were performed on HMC-1, a novel human mast cell line, and on pure populations (i.e., 93 to 99% purity) of human tissue mast cells obtained with mAb and C from dispersed lung (n = 2). Unexpectedly, neither enriched human lung mast cells nor HMC-1 cells bound radiolabeled human rIL-3 specifically. Moreover, human rIL-3 failed to promote uptake of [3H]thymidine, synthesis of histamine, histamine releasability, or changes in expression of mast cell differentiation Ag (YB5B8, CD54/ICAM-1, CD9/p24, CD33/gp67) on either human lung mast cells or HMC-1 cells. It is hypothesized that the fundamental difference in the biologic response to IL-3 between human and murine mast cells is due to a loss during evolution of mast cell high affinity IL-3 binding sites.
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PMID:Failure to detect IL-3-binding sites on human mast cells. 223 Jan 27

Interleukin 3 (IL-3) is required for the survival and proliferation of mouse bone marrow derived mast cells (BMMC). Although interleukin 4 (IL-4) has no direct effect on growth activity, it synergizes with IL-3 in promoting the growth of these cells. The intracellular mechanism by which these ligand-receptor interactions promote mast cell growth are not well documented in the literature. Here we present evidence that both IL-3 and IL-4 have been found to activate protein kinase C (PKC) and phosphatidylinositol turnover in BMMC, in a similar time- and dose-dependent manner, indicating that activation of PKC is not sufficient to induce proliferation in these cells. In this work we addressed the question as to whether the activation of PKC is necessary for mast cell proliferation. Activation of PKC by phorbol myristate acetate causes inhibition of IL-3-mediated growth for the first 72 h of incubation. The inhibition in IL-3-mediated proliferation gradually lessens with the stages of PKC depletion, which is complete after 72 h. The enhancement in phorbol myristate acetate-treated cells grows as PKC is depleted. The inactive phorbol ester, 4-alpha-phorbol, had no effect on proliferation of BMMC. Cells, PKC-depleted by chronical phorbol ester treatment, responded to IL-3 or IL-4 with a significant increase in [3H] thymidine uptake over PKC containing cells stimulated with the same lymphokine. Use of antibodies to these lymphokines showed that the enhanced response of the PKC-depleted BMMC was not due to the additional autocrine production of IL-3 or IL-4 by these cells. The PKC-depleted cells retain the capacity to return to almost normal levels of PKC activity and sensitivity to IL-3 and IL-4, after 72 and 120 h, respectively. These results indicate that PKC plays an important inhibitory role in IL-3- and IL-4-mediated proliferation of BMMC.
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PMID:Protein kinase C plays an inhibitory role in interleukin 3- and interleukin 4-mediated mast cell proliferation. 226 15

Interleukin 3 (IL-3) is a T cell-derived lymphokine that supports the growth and development of hematopoietic cells. Tyrosine phosphorylation has been suggested to play an important role in IL-3-dependent cell proliferation. To test whether a growth factor receptor carrying a tyrosine kinase can be functional in IL-3 dependent cells, we used a retroviral vector to introduce the human EGF receptor into a murine IL-3-dependent pre-mast cell line, IC2. The EGF receptors expressed on the infected clones bind EGF with both high and low affinities. EGF stimulates the infected cells for a short term growth response. In the presence of IL-3 and EGF, infected clones differentiate into more mature mast cells characterized by increases in intracellular granulation and histamine content. This differentiation is reversible when EGF is removed. EGF induces tyrosine phosphorylation of several cellular proteins and the expression of oncogenes c-fos and c-myc, in a manner analogous to IL-3 stimulation. These results indicate that the EGF receptor is functional in the pre-mast IC2 cells; EGF can support short-term proliferation and activates the signals that induce cell differentiation. Thus, EGF receptor-expressing IC2 cells provide a unique cellular system for in vitro study of mast cell differentiation.
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PMID:EGF induces differentiation of an IL-3-dependent cell line expressing the EGF receptor. 253 Oct 81

Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential hematopoietic cell lines in vitro. The molecularly cloned and expressed gene product for this growth factor demonstrates the following activities in vitro: using fresh bone marrow or purified subpopulations of nonadherent cells from murine continuous bone marrow cultures as target cells: stimulation of colony formation by GM-CFUc, mast cell progenitor cells, multipotential granulocyte/erythroid/megakaryocyte/macrophage progenitor cells (CFU-GEMM) colonies, erythroid progenitor cells forming macroscopic bursts (BFUe), and megakaryocyte progenitor cells (CFU-mega). The gene product also supports growth of previously reported mast cell growth-factor-dependent cell lines and several classes of interleukin-3 (IL-3)-dependent hematopoietic progenitor cell lines that are multipotential (neutrophil/basophil/eosinophil or neutrophil/basophil/erythroid); or committed to granulocyte-macrophage, or mast cell/basophil differentiation. The gene product does not detectably support replication of IL-2-dependent murine T-cell lines. The biologic activity of the gene product was inhibited greater than or equal to 90% by rabbit antisera prepared against purified interleukin-3. The data indicate that this T-cell derived lymphokine gene product is biologically very similar to interleukin-3.
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PMID:Molecularly cloned and expressed murine T-cell gene product is biologically similar to interleukin-3. 258 Jul 30

The histology of 17 cases of basal cell carcinoma and dermis next to the carcinoma was observed. The results showed that the mast cell number was markedly increased in the dermis near the basal cell carcinoma. There was an increase in the collagen fibers between the carcinoma and dermis tissues, forming a thin membrane around the carcinoma tissue. These findings suggest that the carcinoma-associated antigen may activate the lymphocytes to produce certain lymphokine which stimulates the proliferation and differentiation of the mast cell precursors. Histamine and other active mediators released from mast cells stimulate fibroblasts to synthesize collagen fibers which form a thin membrane between the carcinoma and dermis. The membrane plays a protective role against tumor dissemination.
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PMID:[Basal cell carcinoma and mast cells]. 263 34

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


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