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 growth-promoting activities of interleukin-10 (IL-10) were assessed in hematopoietic colony-forming assays. We found that IL-10 failed to support the clonal growth of normal and lineage-depleted (Lin-) bone marrow (BM) cells. Furthermore, IL-10 neither enhanced nor suppressed colony formation by eosinophil, neutrophil, or macrophage progenitors when combined with a variety of factors. IL-10 stimulated a modest increase in erythropoietin (Epo)-dependent erythroid colonies but had no effect on the burst-promoting activities of IL-3. However, the combination of IL-10 plus IL-3 resulted in the enhanced growth of mast cell progenitors. In addition to its mast cell stimulating activity, IL-10 promoted the growth of megakaryocyte (Mk) and Mk-mixed colonies when combined with Epo or with Epo plus IL-3, IL-6, or IL-11. Comparative studies showed that the megakaryocyte potentiating activity of IL-10 is roughly equivalent to that of IL-6 and IL-11. In experiments using Thy1loSca1+ stem cells, IL-10 was shown to enhance the number of cells initiating IL-3-dependent colony formation. IL-10 also costimulated increased colony formation when used with IL-3 and another factor such as IL-1, IL-6, and granulocyte colony-stimulating factor (G-CSF). Cellular analysis of the resulting colonies indicated that IL-10 increases the formation of multilineage colonies containing erythrocytes, megakaryocytes, and/or mast cells. The ability of IL-10 to cooperatively regulate various stages of hematopoietic development is discussed.
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PMID:Interleukin-10 promotes the growth of megakaryocyte, mast cell, and multilineage colonies: analysis with committed progenitors and Thy1loSca1+ stem cells. 829 35

In the mouse hematopoietic system, 5-fluorouracil (5-FU) reversibly inhibits the generation of multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage. To determine the effect of 5-FU on mastopoiesis in vitro, bone marrow cells were obtained from mice, cultured, and treated with 5-FU for 14 days in an interleukin-3 (IL-3)-enriched medium. A dose-related inhibitory effect of 5-FU on mastopoiesis was found. When an inhibitory dose (1 microgram/mL) of 5-FU was supplemented to the cultures for only 2, 4, or 8 days and the cells were then recultured without the drug, we observed inhibition of mastopoiesis directly related to the time of exposure of the cells to 5-FU. To determine the effect of 5-FU on mastopoiesis in vivo, bone marrow cells from mice that had received a single intravenous (i.v.) 5-FU injection (150 mg/kg) were cultured. A virtually total absence of mast cells was noted at days 1 and 2 following 5-FU administration. A gradual reappearance of mast cells was later observed. Whether mice were injected with the drug once or with four once-daily (100 mg/kg 5-FU) injections, a similar pattern of delay of mast cell appearance was observed. The findings suggest (1) an irreversible, nonadditive, toxic effect of 5-FU on mast cell precursors and (2) that most or all of the mast cell precursors are nonquiescent cells, continuously activated or cycling. In addition, the use of 5-FU may serve as a unique model system for controlling and studying mastopoiesis in normal mice, rather than the mutated mice currently studied.
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PMID:5-fluorouracil and mast cell precursors in mice. 840 36

We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction profile of marker genes for primitive endoderm (collagen alpha IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and IL-11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.
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PMID:Hematopoietic commitment during embryonic stem cell differentiation in culture. 841 45

The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase). The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbbd-th3/Hbbd-th3) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly.
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PMID:Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. 846 89

LAMA-84, a human leucocytic cell line, which upon establishment was described as having megakaryocytic, erythroid and granulocytic characteristics, was analysed for expression of various differentiation markers. In addition to some of the previously described phenotypic characteristics, this cell line was found to express mRNA for several proteins characteristic for basophilic leucocytes and mast cells. The authors show that LAMA-84 cells express mRNA for the mast cell tryptase, the proteoglycan core protein, carboxypeptidase A and the alpha and beta chains of the high affinity IgE receptor (Fc epsilon RI). The authors examined the potential of LAMA-84 to differentiate in serum-free medium or after DMSO or PMA treatment. Depending on the inducing factor, surface expression of the Fc epsilon RI alpha-chain was increased from 20% to 35-50% of the cells and mRNA levels for tryptase were increased in serum-free medium and after DMSO treatment. LAMA-84 was found to express CD13, CDw17, CD29, CD33, CD40, CD45 and CD117. Furthermore, mRNA for the eosinophil/basophil markers Charcot-Leyden crystal (CLC) protein and the major basic protein (MBP), as well as the erythrocyte differentiation marker alpha-globin, was detected. However, the authors observed only trace amounts of mRNA for another erythroid differentiation marker (glycophorin), trace amounts of the megakaryocytic marker GPIIIa, and no detectable level of GPIb alpha. By comparing the expression pattern of a panel of differentiation markers in LAMA-84, and a second human cell line (KU812) expressing a basophil phenotype, it is evident that these cell lines, which presently are the only two cell lines identified with basophilic characteristics, share a large number of phenotypic characteristics.
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PMID:Characterization of a human basophil-like cell line (LAMA-84). 869 92

The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.
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PMID:Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors. 876 52

Phenotype of P815 mouse mast cells changes markedly during culture in the peritoneal cavity of syngenic BDF1 mice. The cells, cultured for 1 week in the peritoneal cavity of syngenic BDF1 mice, proliferate and express high levels of L-histidine decarboxylase (HDC) and mouse mast cell protease (MMCP)-6 mRNAs, indicating the ability of P815 cells to differentiate toward mature connective tissue mast cells. Peritoneal fluid aspirated from P815-inoculated BDF1 mouse and added to cultured P815 cells in vitro was also found to induce HDC mRNA expression, suggesting that at least some of the humoral factors in the peritoneal fluid induce HDC mRNA transcription. Among the erythroid transcription factors, P815 cells expressed GATA-2 but not GATA-1 mRNA before and after the intraperitoneal incubation. In contrast, the expression of NF-E2 subunit p45 disappeared, while expression of subunit mafK was markedly reduced after incubation. Cotransfection assays using HDC-luciferase reporter and p45 and/or mafK expression constructs showed that NF-E2 affects the transactivation of HDC gene. These results suggest that NF-E2 is also an important transcription factor in mast cell differentiation.
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PMID:Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. 891 Apr 69

Rearrangement of the tal-1 gene is the most frequent clonal marker in childhood T cell acute leukemia. Previously, tal-1 mRNA expression has been observed only in cells of the erythroid, mast cell, and megakaryocytic lineages and in blastic lymphoid cells of normal bone marrow, not in normal lymphocytes or monocytes of the peripheral blood (PB). In this study we addressed the question of tal-1 expression during normal hematopoietic development by performing reverse transcription-polymerase chain reaction (RT-PCR) on RNA from PB cells of 12 healthy donors. Ten of 10 unsorted samples were RT-PCR positive for tal-1 expression. Sorted T cells and monocytes from three donors showed tal-1 RT-PCR products. This is the first direct experimental evidence of tal-1 transcripts in these two normal PB cell types.
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PMID:Transcription of tal-1, a putative oncogene playing an important role in childhood T-ALL, can be shown in normal peripheral blood cells by a highly sensitive RT-PCR assay. 921 39

Shp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two Src homology 2 (SH2) domains. A negative regulatory role of Shp-1 in hematopoiesis has been strongly implicated by the phenotype of motheaten mice with a mutation in the Shp-1 locus, which is characterized by leukocyte hypersensitivity, deregulated mast cell function, and excessive erythropoiesis. A targeted deletion of 65 amino acids in the N-terminal SH2 (SH2-N) domain of Shp-2 leads to an embryonic lethality at midgestation in homozygous mutant mice. To further dissect the Shp-2 function in hematopoietic development, we have isolated homozygous Shp-2 mutant embryonic stem (ES) cells. Significantly reduced hematopoietic activity was observed when the mutant ES cells were allowed to differentiate into embryoid bodies (EBs), compared to the wild-type and heterozygous ES cells. Further analysis of ES cell differentiation in vitro showed that mutation in the Shp-2 locus severely suppressed the development of primitive and definitive erythroid progenitors and completely blocked the production of progenitor cells for granulocytes-macrophages and mast cells. Reverse transcriptase PCR analysis of the mutant EBs revealed reduced expression of several specific marker genes that are induced during blood cell differentiation. Stem cell factor induction of mitogen-activated protein kinase activity was also blocked in Shp-2 mutant cells. Taken together, these results indicate that Shp-2 is an essential component and primarily plays a positive role in signaling pathways that mediate hematopoiesis in mammals. Furthermore, stimulation of its catalytic activity is not sufficient, while interaction via the SH2 domains with the targets or regulators is necessary for its biological functions in cells. The in vitro ES cell differentiation assay can be used as a biological tool in dissecting cytoplasmic signaling pathways.
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PMID:A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development. 927 25

To examine the relation between receptor expression and differentiation of hematopoietic cells, we produced transgenic mice that constitutively expressed the human granulocyte-macrophage colony stimulating factor (hGM-CSF) receptor at almost all stages of hematopoietic cell development. The high-affinity GM-CSF receptor is species specific, allowing analysis of the specific effects of hGM-CSF in our mouse model. Proliferation and differentiation of hematopoietic progenitor cells from transgenic mice were analyzed by means of methylcellulose colony-forming assay and in vivo treatment with hGM-CSF, respectively. We found that hGM-CSF supported various types of colonies, including granulocyte-macrophage, mast cell, megakaryocyte, blast cell, and mixed hematopoietic colonies, whereas mouse GM-CSF supported only granulocyte-macrophage colonies. In addition, hGM-CSF generated erythrocyte colonies in the absence of erythropoietin. Furthermore, in vivo administration of hGM-CSF to transgenic mice resulted in a dose-dependent increase in reticulocytes and white blood cells in the peripheral blood. The spleens of the mice showed gross enlargement, mainly caused by an increase of erythroid cells and their progenitors. Taken together, these results indicate that hGM-CSF receptor-mediated signals can support the growth of cells of all hematopoietic cell lineages if this receptor is present on the cell surface. This implies that the differentiation of hematopoietic progenitor cells is not determined by exogenous cytokine stimulation (instruction model) but by an intrinsic cell program in which cytokines simply select cells that express the appropriate receptor (stochastic model).
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PMID:Human granulocyte-macrophage colony-stimulating factor (hGM-CSF)-dependent in vitro and in vivo proliferation and differentiation of all hematopoietic progenitor cells in hGM-CSF receptor transgenic mice. 944 May 51


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