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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have established permanent lines of nonadherent cells from fresh normal mouse bone marrow in media containing pokeweed mitogen-stimulated spleen cell conditioned medium (PWSCM). These lines continuously produced erythropoietic progenitor cells (detected by their ability to form erythroid bursts in semi-solid medium containing erythropoietin) together with cells having characteristics of the mast cell lineage (as demonstrated by metachromatic staining with toluidine blue, histamine content and membrane receptors for IgE). Sixteen such cell lines have been established in sixteen attempts. Cloning experiments were carried out to determine the nature of the progenitor cell(s) responsible for the permanence of these cultures. When cells were cultured in methylcellulose medium containing PWSCM, colonies were observed which reached macroscopic size after 4 weeks of incubation. Replating of individual primary colonies resulted in secondary colony formation, indicating the presence of progenitor cells with self-renewal potential. Forty-seven primary colonies were picked and their cells were suspended in liquid culture medium containing PWSCM. Of these, twenty-one could be expanded to establish permanently growing sublines. Sixteen of these sublines were found to be composed of both erythroid progenitors and mast cells. In five sublines only mast cells could be seen; none of the sublines appeared to be purely erythroid. Karyotypic analysis of mast cells and of erythroid cells of seven sublines derived from individual colonies which arose in cocultures of male and female cells revealed that the mast cells and erythroid cells were both of the same sex in each of the seven sublines; this demonstrates the single cell origin of each colony and of the two lineages derived from it. We conclude that these nonadherent, factor-dependent cell lines are maintained by self-renewal and differentiation of bipotential progenitor cells apparently restricted to the erythroid and mast cell lineages.
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PMID:A self-renewing, bipotential erythroid/mast cell progenitor in continuous cultures of normal murine bone marrow. 293 43

B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7-20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors.
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PMID:Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells. 349 34

Multipotential hematopoietic progenitor cell lines have been established from nonadherent cell populations removed from continuous mouse bone marrow cultures. Clonal sublines of lines B6SUtA or B6JUt derived from single cells formed mixed colonies containing erythroid cells, neutrophil-granulocytes, and basophil/mast cells in semisolid medium containing erythropoietin and conditioned medium from pokeweed mitogen-stimulated spleen cells. Each of several subclones of cell line Ro cl formed colonies containing eosinophils, neutrophil-granulocytes, and basophil/mast cells in semisolid medium. Multipotentiality was maintained in vitro for over 2 1/2 years. In contrast, cell line 32D formed basophil/mast cell colonies with no detectable differentiation to other pathways. Multipotential cell lines did not produce detectable spleen colonies (CFUs) in vivo, nor did intravenous inoculation of up to 5 X 10(7) cells protect lethally irradiated mice from bone marrow failure. Newborn and adult mice inoculated with 5 X 10(7) cells showed no detectable leukemia or solid tumors after one year. Both multipotential and committed basophil/mast cell lines demonstrated absolute dependence upon a source of a growth factor(s) found in medium conditioned by WEHI-3 cells. These cell lines should be of value in studies of the regulation of hematopoietic stem cell differentiation in vitro.
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PMID:Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. 657 62

We analyzed the differentiation of murine hemopoietic colonies derived from paired progenitors in culture. Single progenitors were isolated by use of a micromanipulation technique from blast cell colonies cultured from the spleens of 5-fluorouracil-treated mice. Eighteen to 24 hr later, the paired progenitors were separated with a micromanipulator and cultured in methylcellulose medium containing erythropoietin and pokeweed-mitogen spleen cell conditioned medium. Six to nine days later, the two colonies derived from the paired progenitors were individually picked and differential counts were performed by using May-Grunwald-Giemsa stain. The abbreviations used here are n, neutrophil; m, macrophage; e, eosinophil; mast, mast cell; M, megakaryocyte; E, erythrocyte. Of a total of 387 pairs that could be evaluated, 68 were pairs of colonies consisting of dissimilar combinations of cell lineages such as m-nmmastEM, M-nmmastEM, nm-nmmastEM, nmmastM-nmmastEM, M-nmmastM, nmmast-nmmastM, nm-nmmastE, M-nmM, n-nmM, mM-nmM, m-nmmast, nm-nme, me-nm, mM-nm, n-ne, m-mmast, m-mM, M-nm, M-mM, E-nm, m-nm, M-m, etc. Thirty-nine were homologous pairs revealing identical lineage combinations such as nmmastEM, nmmastM, nmmast, mmastEM, nmEM, nme, nmM, mM, and nm lineages. However, in members of some of these pairs, the proportions of the individual cell lineages were significantly different. The remainder were pairs of single lineage colonies. Paired progenitors obtained from the stem cell colonies of normal mice also revealed homologous and nonhomologous expression of the cell lineages. Comparison of lineage expression in colonies derived from single progenitors with the sum of lineages expressed in pairs of colonies derived from single progenitors indicated that the diversity was not due to injury inflicted by micromanipulation. These observations provide experimental data in support of stochastic mechanisms of stem cell differentiation.
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PMID:Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. 2369 79

The hematopoietic microenvironment in Steel mutant mice does not support erythropoiesis, megakaryocytopoiesis, or mast cell generation. The question of whether Steel hematopoietic progenitors are present in normal numbers has never been convincingly addressed. In this report, Sl/Sld marrow cells were assessed for long-term competitive repopulation ability in vivo and for short-term growth in vitro. In vivo repopulation assays indicate that the Sl/Sld progenitors are at a distinct disadvantage when they compete against congenic genetically marked +/+ cells in a +/+ host. On the other hand, the Steel erythroid colony-forming cells (CFU-E) respond normally to erythropoietin (Epo) in vitro and are present at normal frequency. Because the Steel marrow is less cellular than normal marrow, the absolute number of CFU-E is decreased. Results suggest that the absence of membrane-bound Steel factor in the mutant donor has a direct effect on Steel hematopoietic progenitors, which is not alleviated during growth for over 6 months in a normal microenvironment. The anomaly does not seem to directly affect the frequency of more mature adult erythroid progenitors.
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PMID:Sl/Sld hematopoietic progenitors are deficient in situ. 750 59

We have studied the frequency of colony-forming cells (CFC) in fetal and neonatal blood in comparison with adult blood and marrow. Fetal or neonatal blood contains at least as many CFC as adult marrow and higher numbers of the more primitive CFC--those CFC (mixed-cell CFC) giving rise to colonies composed of erythroid and myeloid cells. CD34+ cord blood cells (selected by one of several means) proliferate in culture over time and generate more CFC (from pre-CFC) and differentiated cells in response to stem cell factor (SCF) plus different hematopoietic growth factors. For its effect, SCF requires the synergistic action of erythropoietin (Epo), granulocyte colony-stimulating factor (G-CSF), or interleukin-3 (IL-3). In the presence of Epo or G-CSF, CFC and differentiated cells are generated for 15 days and are mainly erythroid or granulocytic, respectively. In contrast, SCF plus IL-3 generate multilineage CFC and differentiated cells for more than 1 month. When the conditions for these long-term suspension cultures were optimized, CFC and differentiated cells were generated for more than 2 months. At this time, CFC were no longer detectable, but cells continued to be generated, and the cells had a mast cell phenotype. These cells have been maintained and propagated for more than 8 months in the presence of IL-3 and SCF and may represent a useful tool to study human mast cell differentiation.
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PMID:Stem cell factor and the amplification of progenitor cells from CD34+ cord blood cells. 752 76

Granulocyte-macrophage colony-stimulating factor (GM-CSF) mainly stimulates proliferation and maturation of myeloid progenitor cells. Although the signal transduction pathways triggered by GM-CSF receptor (GMR) have been extensively characterized, the roles of GMR signals in differentiation have remained to be elucidated. To examine the relationship between receptor expression and differentiation of hemopoietic cells, we used transgenic mice (Tg-mice) that constitutively express human (h) GMR at almost all stages of hemopoietic cell development. Proliferation and differentiation of hemopoietic progenitors in bone marrow cells from these Tg-mice were analyzed by methylcellulose colony formation assay. High affinity GMR interacts with GM-CSF in a species-specific manner, therefore one can analyze the effects of hGMR signals on differentiation of mouse hemopoietic progenitors using hGM-CSF. Although mouse (m) GM-CSF yielded only GM colonies, hGM-CSF supported various types of colonies including GM, eosinophil, mast cell, erythrocyte, megakaryocyte, blast cell, and mixed hemopoietic colonies. Thus, the effects of hGM-CSF on colony formation more closely resembled mIL-3 than those of mGM-CSF. In addition, hGM-CSF generated a much larger number of blast cell colonies and mixed cell colonies than did mIL-3. hGM-CSF also generated erythrocyte colonies in the absence of erythropoietin. Therefore, GM-CSF apparently has the capacity to promote growth of cells of almost all hemopoietic cell lineages, if functional hGMR is present.
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PMID:A human GM-CSF receptor expressed in transgenic mice stimulates proliferation and differentiation of hemopoietic progenitors to all lineages in response to human GM-CSF. 754 29

Interleukin 12 (IL-12: natural killer cell stimulatory factor, NKSF; cytotoxic lymphocyte maturation factor, CLMF) was studied for its effect on colony formation and lineage expression of low-density bone marrow cells from 5-fluorouracil-treated mice, and of sorted stem cells using a semi-solid culture assay in the absence or presence of IL-3, IL-11, Steel factor (SF) and erythropoietin. IL-12 did not support colony formation as a single factor, nor in the presence of IL-11 or SF. In IL-3-containing cultures, IL-12 slightly enhanced neutrophilic and monocyte differentiation. Both SF and IL-11 synergized with IL-3 to increase the percentage of multilineage colonies and the number of colonies containing erythrocytes, megakaryocytes, neutrophils, eosinophils, monocytes/macrophages, and blast cells, but not mast cells. In the presence of IL-3 + IL-11, IL-12 greatly enhanced neutrophil, megakaryocyte, erythrocyte, and mast cell development. In IL-3 + SF-containing cultures, IL-12 further increased colony numbers and a higher percentage of colonies expressed neutrophilic, megakaryocytic, erythroid, monocytic, blast cell, and/or mast cell lineages. Colony size and the presence of eosinophils in colonies were unaffected by IL-12 addition. These effects of IL-12 could not be reversed by antibodies against interferon-gamma. Our data show that IL-12 may act as a synergistic factor, stimulating multilineage expression of hemopoietic stem cells, probably via a direct action. The observed activity of IL-12, however, required the presence of a least two factors, i.e. either IL-3 + IL-11, or IL-3 + SF.
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PMID:Interleukin-12 enhances interleukin-3 dependent multilineage hematopoietic colony formation stimulated by interleukin-11 or steel factor. 769 Apr 39

We have studied the frequency of colony forming cells (CFC) in fetal and neonatal blood in comparison with adult blood and marrow. Fetal/neonatal blood contains at least as many CFC as adult marrow and higher numbers of the more primitive CFC--those CFC giving rise to colonies composed of erythroid and myeloid cells. CD34+ cord blood cells (selected either by sorting, panning or affinity chromatography) proliferate in culture over time and generate more CFC (from pre-CFC) and differentiated cells in response to Steel factor plus different hematopoietic growth factors. Steel factor is unable to stimulate cell growth by itself under serum-deprived conditions and requires the synergistic action of erythropoietin (Epo), granulocyte colony stimulating factor (G-CSF) or interleukin 3 (IL-3). In the presence of Epo or G-CSF, CFC and differentiated cells are generated for 15 days and are mainly erythroid or granulocytic, respectively. In contrast, Steel factor plus IL-3 generates multilineage CFC and differentiated cells for more than one month. When the conditions for these long-term suspension cultures were optimized (37 degrees C, regular refeeding with fresh growth factors and media without changing the flask), CFC and differentiated cells were generated for more than two months. At this time, CFC were no longer detectable and all cells had a mast cell phenotype. These cells have been maintained and propagated for more than eight months in the presence of IL-3 and Steel factor and may represent a useful tool to study human mast cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aspects of the biology of the neonatal hematopoietic stem cell. 769 29

Mast cell neutral proteases are the most precise markers of heterogeneity among human mast cells. Two types of human mast cells have been recognized. MCTC cells contain tryptase together with chymase, cathepsin-G like protease, and mast cell carboxypeptidase; MCT cells contain tryptase, but lack the other neutral proteases present in MCTC cells. All mast cells develop from hemopoietic stem cells. In vitro procedures for studying mast cell growth have been developed, using the major human mast cell growth factor, stem cell factor (SCF, also called Kit-ligand). Cultures of hemopoietic progenitor cells in the presence of SCF alone result in selective differentiation to mast cells. The same progenitor cells can be induced to differentiate into other lineages when SCF is used with various lineage-specific colony-stimulating factors such as erythropoietin for erythrocytes. Mast cell development from hematopoietic progenitors may represent a "default pathway," occurring optimally in a permissive microenvironment such as skin, bowel, and lung. The presence or absence of certain cytokines in blood and bone marrow may create a non-permissive environment, thus the absence of granulated mast cells in such locations.
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PMID:Human mast cell heterogeneity. 772 Oct 78


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