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 t(14;18) of human follicular B cell lymphoma translocates the Bcl-2 gene into the Ig H chain locus and markedly deregulates Bcl-2 expression. We sought to determine if Bcl-2 could be directly implicated in a growth-factor pathway. Consequently, we introduced a retrovirus containing the murine Bcl-2 gene (N2-M-Bcl-2) or the parental retrovirus (N2) into a series of factor-dependent hemopoietic cell lines. Overexpressed Bcl-2 resulted in no long term IL-2, IL-3, or IL-6 independent clones, indicating that Bcl-2 could not spare the need for a specific ligand-receptor interaction. However, Bcl-2 did extend the short term survival of IL-3-dependent cell lines after factor deprivation. Although viable, IL-3-deprived pro B lymphocytes (FL5.12) bearing N2-M-Bcl-2 were in Go, and deregulated Bcl-2 did not obviously influence cell-cycle progression. Bcl-2 predominant effects were to delay the onset of cell death and to modestly augment viable cell growth in the first 48 h after IL-3 deprivation. This death sparing was associated with increased levels of Bcl-2 RNA and protein in factor-deprived cells possessing N2-M-Bcl-2. This result was not restricted to prolymphocytes because an IL-3-dependent mast cell line (32D) as well as a promyeloid line (FDC-P1) demonstrated the same response to Bcl-2. Moreover, the effect was not limited to the IL-3/IL-3R signal transduction pathway in that promyeloid cells maintained in granulocyte-macrophage-CSF or IL-4 displayed a similar response. Yet, Bcl-2-enhanced cell survival was not universal as an IL-2-dependent T cell line, and an IL-6-dependent myeloma line demonstrated no consistent effect upon IL withdrawal. Thus, Bcl-2 appears to interfere with cell death but in a cell type and/or factor-restricted fashion.
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PMID:Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. 218 93

A role for second messenger-regulated protein kinases in the early post-IL-3 receptor signal transduction pathway was investigated in the mast cell/megakaryocyte line R6-XE.4. The activity of the calcium- and phospholipid-dependent protein kinase C (PKC) was assessed by the ability of the enzyme to phosphorylate histone H1 in the presence of calcium, diacylglycerol, and phosphatidylserine or after proteolytic activation of PKC with trypsin. In high serum-supplemented cells, but not in cells that were preincubated in serum-deficient media for 6 h, subsequent treatment for 15 min with synthetic IL-3 (10 micrograms/ml) caused up to a sixfold increase in the calcium- and lipid-stimulated histone H1 phosphorylating activity of particulate-associated PKC after fractionation on MonoQ. However, there was no corresponding reduction of cytosolic PKC activity. Therefore, IL-3 appeared to modify the activity of preexisting membrane-associated PKC rather than eliciting its recruitment from the cytoplasm in R6-XE.4 cells. This was in contrast to the situation with FDC-P1 cells, where IL-3 induced PKC translocation. IL-3 also stimulated a cytosolic protein kinase that phosphorylated a synthetic peptide patterned after a phosphorylation site in ribosomal protein S6, but this IL did not alter the activity of cAMP-dependent protein kinase.
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PMID:IL-3-induced activation of protein kinases in the mast cell/megakaryocyte R6-XE.4 line. 230 40

A semi-purified fraction extracted from fetal calf bone marrow was previously shown to contain a tetrapeptide N-Ac-Ser-Asp-Lys-Pro which inhibits in mice, hematopoietic stem cell entry into the cell cycle. This peptide however, did not exhibit any effect on either IL-3 nor GM-CSF dependent cell growth. We report herein that a semi-purified fraction also contains another activity which is antagonistic to IL-3. Addition of the fraction in vitro decreased IL-3 dependent mast cell colony formation. Growth of IL-3 dependent cell lines (DA-1 and FDC-P2) was also suppressed. No effect was observed in the same dose range on granulocyte-macrophage colony formation nor on IL-3 independent cell growth.
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PMID:Suppression of mast cell colony formation by a low molecular weight fraction of fetal calf bone marrow extract. 261 66

A series of murine interleukin 3 (IL-3)-dependent hemopoietic cell lines was studied for the capacity to produce interleukin 6 (IL-6) in vitro. These included a bone marrow-derived mast cell line (L138.8A) and several early myeloid cell lines described in the literature (DA-1, DA-3, NFS-60, NFS-78, FDC-P1, FDC-P2, FDC-PmixA4, and 32Dcl.23). All of these cell lines produced growth factor activity for IL-6-dependent hybridoma cells (7TD1), which was completely neutralized by the monoclonal anti-IL-6-antibody 6B4. IL-6 expression was also evident at the mRNA level using a murine IL-6-specific cDNA probe. In 32Dcl.23 cells (2 x 10(5)/ml) stimulated for 24 hr with serial dilutions of purified murine IL-3, a positive correlation was found between the IL-3 dose and the amount of IL-6 measured in the conditioned media. At 24 hr this correlation was not evident at the mRNA level. However, prolonged exposure of 32Dcl.23 cells (up to 72 hr) to either a high (60 U/ml) or a low IL-3 concentration (1 U/ml) revealed a time-dependent increase and decrease, respectively, of IL-6 mRNA levels. At both IL-3 concentrations 32Dcl.23 cells remained in a fully viable and proliferative state. The influence of IL-3 on IL-6 release could be specifically counteracted by anti-IL-3-antiserum. IL-6 added alone or in concert with IL-3 did not stimulate 32Dcl.23 proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin 3 mediates interleukin 6 production in murine interleukin 3-dependent hemopoietic cells. 263 55

Post 5-fluorouracil-treated murine marrow cells were infected with a retroviral vector (MPZen) bearing a multi-potential colony stimulating factor (Multi-CSF) cDNA insert and then transplanted into lethally irradiated syngeneic recipients to study the effects of autocrine production of Multi-CSF in normal hematopoietic cells. Extremely high levels (14,000 U/mL) of Multi-CSF were detected in the sera and in media conditioned by various hematopoietic tissues of the transplanted animals. While spleen, peritoneal, and peripheral blood cellularity increased approximately 10-fold, 10-fold, and 50-fold, respectively, bone marrow cellularity decreased twofold. Progenitor numbers were depressed twofold in the bone marrow but elevated more than 100-fold in the spleen and peritoneum. The majority (80%) of transplanted mice died within 5 weeks of transplantation and showed extensive neutrophilic infiltration of the spleen, lung, liver, and muscle, often with mast cell foci; a phenomenon also seen in the skin and intestine. Neither the infected cells from hematopoietic tissues of the primary mice, nor autonomous mast cell-lines that grew from these cells in liquid culture produced any overt disease when transplanted into normal or sublethally irradiated secondary recipients. In contrast, injection into mice of autonomous FDC-P1 cells transformed by the same retroviral construct led to tumor formation in vivo within 4 weeks. Thus, dysregulated Multi-CSF expression by normal hematopoietic cells produces a fatal but nonneoplastic myeloproliferative syndrome.
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PMID:Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression. 265 57

Two distinct hemopoietic growth factors, interleukin 3 (IL-3) and erythropoietin (EPO), support the growth and development of erythroid cells in a sequential manner in vitro. Stimulation of multipotential stem cells by IL-3 appears to develop committed erythroid progenitor cells that respond to EPO. When several murine IL-3-dependent cell lines were assayed for their ability to respond to EPO, the growth and survival of the three cell lines showing the profiles of either myeloid or mast cell lineage (IC-2, DA-1, FDC-P2) were stimulated by EPO in a dose-dependent fashion. To determine whether the biologic effects were mediated through the specific receptors for EPO, we performed binding experiments on these cells with radioiodinated EPO. All of these cells displayed significant levels of specific binding for EPO. Among a family of hemopoietic growth factors, only unlabeled EPO was able to compete for the binding of radioiodinated EPO to the cells. Analysis of the binding data revealed the existence of a single case of binding sites in extremely low abundance. IC-2 cells were used to study the effects of IL-3 on the regulation of expression of EPO receptors. It was demonstrated that a decrease in IL-3 concentration in the culture medium increased the responsiveness to EPO and the amount in specific binding of EPO as well. These results suggest that some IL-3-dependent cell lines have functional EPO receptors and their expression may be modulated by IL-3.
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PMID:Expression of the functional erythropoietin receptors on interleukin 3-dependent murine cell lines. 282 92

We previously described the interleukin 3 (IL-3)-dependent cell line, M1-A5, which has both natural cytotoxic (NC) and suppressor cell activities, the latter of which is mediated, in part, by the release of two cytokines which activate suppressor cells from unprimed lymphoid precursor cells. In this study we have compared the M1-A5 cell line with four other IL-3-dependent cell lines to determine whether these dual activities are universally associated with IL-3 dependence and to test the hypothesis that there is a direct relationship between the cytotoxic and the suppressive activities. The cell lines tested were a bone marrow derived Dexter culture derived line (FDC-P1), two Moloney leukemia virus induced leukemias (DA-1 and DA-3), and a mast cell line (PT18(A17]. All lines were dependent on IL-3 for survival but FDC-P1, DA-1, and DA-3 showed varying degrees of short-term proliferation in granulocyte-macrophage colony stimulating factor (GM-CSF). The cell lines all expressed asialo GM1 and Ly-5 surface markers but differed with respect to other markers. DA-1 expressed MAC-1, FDC-P1 and DA-3 expressed Thy-1, and PT18(A17) expressed receptors for the Fc portion of IgE. The cell lines varied greatly in their cytotoxic activity against WEHI-164. FDC-P1, DA-1, and PT18(A17) had low NC activity. DA-3 had consistently high activity, greater than that seen with M1-A5 cells. However, none of the cell lines secreted constitutively a suppressor cell inducing factor (SIF). In addition, it was demonstrated that recombinant murine TNF did not activate suppressor cells capable of inhibiting antibody synthesis and that anti-TNF did not block SIF activity, thus suggesting that TNF contamination of the M1-A5 derived SIF preparation is not responsible for the induction of suppressor cells. We conclude that suppressor cell inducing factors are not universally secreted by IL-3-dependent cell lines, that there is no correlation between NC and SIF activity, and that the dual activities of M1-A5 cells are not mediated by TNF.
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PMID:Secretion of a suppressor cell inducing factor by an interleukin 3-dependent cell line with natural cytotoxic activity. III. Comparison with other interleukin 3-dependent cell lines. 297 53

The human epidermal growth factor-receptor (EGF-R) was introduced into primary mouse bone marrow cells (BMC), utilizing retrovirus mediated gene transfer. Cultivation of infected BMC in the presence of interleukin-3 (IL-3) led to the outgrowth of IL-3 dependent myeloid cells, which efficiently expressed functional EGF-R, exhibiting its two characteristic affinity states. EGF acts on these cells synergistically with IL-3 in stimulating DNA synthesis and cell proliferation even under IL-3 saturation conditions. However, EGF was not sufficient to replace the requirement for IL-3. In contrast, EGF was able to maintain proliferation of a factor-dependent hemopoietic cell line (FDC-P1) infected with the EGF-R retrovirus in the absence of IL-3, but these cells did not respond to EGF in the presence of IL-3. No influence of EGF on IL-3 induced mast cell differentiation of BMC expressing the EGF-R could be observed by histological criteria. These data show that the expression of EGF-R alone is not sufficient to induce or maintain cell proliferation in IL-3 dependent bone marrow derived cells, although it can do so in established hemopoietic cell lines.
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PMID:Expression of functional human EGF receptor on murine bone marrow cells. 305 64

Several mouse IL 3-dependent cell lines, IC2, LT4, FDC-P2, and PB-3C, derived from spleen or bone marrow cells were shown to express low affinity receptors for IL 2 (Kd; 0.5 to 8 X 10(-8) M). High affinity receptors for IL 2 were not detected on the IL 3-dependent cells within the experimental limitation of this study. The clones did not respond to IL 2 at all at the concentration as high as 25 micrograms/ml. The number of the receptors expressed on those clones was estimated to be 0.2 to 2 X 10(5)/cell, which is comparable with the number of those on IL 2-dependent T cell clones. Expression of IL 2 receptor was confirmed in mRNA levels for both IC2 and LT4 cells. A relatively low level expression of one (4.5 Kb) of four IL 2 receptor mRNA species was observed with those IL 3-dependent clones compared with IL 2-dependent T cells. It seems that these low affinity receptors may be expressed on IL 3-dependent cells that undergo differentiation or maturation in mast cell and some myeloid cell lineages.
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PMID:Expression of interleukin 2 receptors on interleukin 3-dependent cell lines. 307 7

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


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