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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetic changes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) on hemopoietic cells were assessed in physiological conditions by administering GM-CSF (8 micrograms/kg per d) for 3 d to nine patients with solid tumors and normal bone marrow (BM), before chemotherapy. GM-CSF increased the number of circulating granulocytes and monocytes; platelets, erythrocytes, lymphocyte number, and subsets were unmodified. GM-CSF increased the percentage of BM S phase BFU-E (from 32 +/- 7 to 79 +/- 16%), day 14 colony-forming unit granulocyte-macrophage (CFU-GM) (from 43 +/- 20 to 82 +/- 11%) and day 7 CFU-GM (from 41 +/- 14 to 56 +/- 20%). The percentage of BM myeloblasts, promyelocytes, and myelocytes in S phase increased from 26 +/- 14 to 41 +/- 6%, and that of erythroblasts increased from 25 +/- 12 to 30 +/- 12%. This suggests that GM-CSF activates both erythroid and granulomonopoietic progenitors but that, among the morphologically recognizable BM precursors, only the granulomonopoietic lineage is a direct target of the molecule. GM-CSF increased the birth rate of cycling cells from 1.3 to 3.4 cells %/h and decreased the duration of the S phase from 14.3 to 9.1 h and the cell cycle time from 86 to 26 h. After treatment discontinuation, the number of circulating granulocytes and monocytes rapidly fell. The proportion of S phase BM cells dropped to values lower than pretreatment levels, suggesting a period of relative refractoriness to cell cycle-active antineoplastic agents.
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PMID:Kinetics of human hemopoietic cells after in vivo administration of granulocyte-macrophage colony-stimulating factor. 264 33

Previous in vitro investigations on enriched human hematopoietic progenitors have led to the conclusion that the purified recombinant multipoietins, interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can alone induce the formation of colonies from a variety of multipotent and lineage committed progenitors. Since fetal calf serum was included in these cultures and itself might contain growth factors or other cofactors, we re-examined the actions of the CSFs in serum-deprived conditions. Results show that both the multipoietins are inadequate stimuli of colony formation. At maximal concentrations IL-3 alone induces only 25% of the granulocyte and macrophage colony-forming units (CFU-G and CFU-M) produced by a T-cell conditioned medium that contains a mixture of CSFs. When IL-3 was added at the initiation of the cultures and erythropoietin (ep), G-CSF, or M-CSF added on day 3, almost full recovery of erythroid, granulocytic, and monocytic colonies, respectively, was obtained. Similar results were obtained with GM-CSF except that fewer erythroid colonies were recovered at high concentrations, and almost maximal CFU-M proliferation could be induced. These results show that in serum-deprived conditions, the multipoietins must be combined with lineage specific CSFs for full progenitor expression.
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PMID:Combinations of recombinant colony-stimulating factors are required for optimal hematopoietic differentiation in serum-deprived culture. 264 85

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been described as a multilineage growth factor that induces in vitro colony formation from erythroid burst-forming units (BFU-E), eosinophil colony-forming units (CFU-Eo), and multipotential CFU (CFU-GEMM) as well as from granulocyte-macrophage CFU (CFU-GM), granulocyte CFU (CFU-G), and macrophage CFU (CFU-M). In this paper we provide evidence indicating that GM-CSF, when tested for its stimulating capacities expressed upon highly enriched hematopoietic progenitor cells (CD34+/monocyte-depleted), is unable to induce colonies from CFU-GM, CFU-G, or CFU-M. Only BFU-E, CFU-Eo, and CFU-GEMM were stimulated, and thus GM-CSF induces a similarly restricted spectrum of progenitor cells as does recombinant human interleukin 3 (IL-3). We then compared the relative stimulating potencies of GM-CSF and IL-3 by measuring colony numbers of CFU-GEMM, BFU-E, and CFU-Eo generated from CD34+ progenitor cells. IL-3 and GM-CSF as single factors were equally active in stimulating CFU-GEMM, but the combination of both factors produced additive stimulative effects upon CFU-GEMM. IL-3 was a more potent stimulus of BFU-E, and GM-CSF was the more active stimulating factor for CFU-Eo. We conclude that GM-CSF and IL-3, although stimulating the outgrowth of identical types of progenitor cells, particularly differ as regards their comparative quantitative efficiency of stimulation.
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PMID:Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates immature marrow precursors but no CFU-GM, CFU-G, or CFU-M. 264 58

To determine the extent accessory cells mediate the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on human hemopoietic progenitors in vitro, we added this hemopoietin to liquid cultures of single CD34-positive marrow cells. These were selected on a fluorescence-activated cell sorter using the HPCA-1 (My10) antibody. Myeloid, erythroid and a few mixed clones developed in 13% of wells in the apparent absence of accessory cells at the beginning of culture. Although accessory cells were generated quickly from the myeloid progenitors and could have mediated the action of rhGM-CSF, this was not the case in the majority of the erythroid clones in which no other cell types were recorded. We conclude that rhGM-CSF can act directly on a subset of erythroid progenitors and probably induces a substantial number of myeloid clones directly.
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PMID:Effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on single CD34-positive hemopoietic progenitors from human bone marrow. 264 75

Human acute erythroleukaemia arises from the inability of the haemopoietic stem cell to differentiate. K 562 cell line provides a homogeneous population of primitive erythroleukaemic cells that are at the same point of differentiation. The effect of human recombinant granulocyte-macrophage colony-stimulating factor and human recombinant erythropoietin on the differentiation of K 562 clonogenic cells was studied. Cells were cultured in methylcellulose culture for 5 days at 37 degrees C in humidified atmosphere containing 5% CO2 in air and scored for erythroid differentiation by benzidine staining. A combination of both growth factors induced erythroid differentiation in more than 80% of K 562 clonogenic cells. This combination may be useful in the treatment of patients with erythroleukaemia.
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PMID:Cooperative effects of human recombinant granulocyte-macrophage colony stimulating factor and human recombinant erythropoietin in inducing erythroid differentiation of the human erythroleukaemia cell line K 562 clonogenic cells. 264 83

To clarify the defective erythropoiesis in eight patients with Diamond-Blackfan anemia, we studied their bone marrow response in vitro to recombinant human interleukin-3 (IL-3) and recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). In an erythropoietin-containing assay system, specimens from six of the eight patients yielded low numbers of erythroid colonies compared to control values, and in five of these no erythropoietin dose-response could be elicited. Addition of IL-3, GM-CSF or both to cultures from the six patients had no effect on CFU-E-derived colonies. In contrast, IL-3 but not GM-CSF induced a marked increase in the number (183%) and size of the BFU-E-derived colonies in five of the six cases and partially corrected the impaired dose-response to erythropoietin in four. Bone marrow from the other two patients yielded numbers of CFU-E and BFU-E colonies comparable to controls and manifested similar increments in colonies with increasing concentrations of erythropoietin. When IL-3 was added to these cultures, further increments were observed in the number and size of BFU-E colonies. We conclude that IL-3 enhanced the marrow erythropoiesis in most of the patients and exerted a corrective effect on the aberrant colony formation in the presence of erythropoietin. The data raise the possibility of IL-3 as a therapeutic agent in Diamond-Blackfan anemia.
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PMID:Diamond-Blackfan anemia: promotion of marrow erythropoiesis in vitro by recombinant interleukin-3. 264 68

Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferation and/or differentiation is undefined. In the present study, the response of erythroid precursors at different stages of differentiation to Epo was examined. Erythroblasts were derived from adult blood erythroid progenitors (BFU-E) at day 7 or day 10 of culture. [Cac] was measured in individual Fura-2 loaded cells with fluorescence microscopy coupled digital video imaging. The dynamic range (Rmax/Rmin) of intracellular Fura-2 was similar to that measured in free solution, suggesting insignificant amounts of intracellular Ca insensitive forms of Fura-2. Baseline [Cac] of erythroid cells calculated with an in vitro calibration method was 44 +/- 4 nmol/L and with an in vivo method was 46 +/- 4 nmol/L. Treatment of day 7 BFU-E derived erythroblasts with Epo resulted in no significant increase in [Cac]. In contrast, in more mature erythroblasts (day 10 of culture), Epo stimulated a large increase in [Cac] from 49 +/- 11 nmol/L at baseline to 279 +/- 47 nmol/L. This [Cac] increase occurred in phosphate buffered saline (PBS) containing no added calcium. The increase in [Cac] persisted for 18 minutes and was dose dependent. Day 7 and day 10 control cells treated with either insulin or media showed no significant change in [Cac] during 18 minutes of observation. Our data demonstrate that early (day 7) and late (day 10) erythroblasts display different responses to Epo, at least in terms of intracellular Ca++ fluxes. The differential [Cac] response observed in early and late erythroid precursors to growth factor stimulation suggests that [Cac] may be an important signal in cell differentiation.
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PMID:Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation. 264 70

The presence of heterogeneous erythroid progenitor cells, contaminant cells, or serum may alter erythroid colony development in vitro. To obtain highly purified colony-forming units-erythroid (CFU-E), we cultured partially purified human blood burst-forming units-erythroid (BFU-E) in methylcellulose with recombinant human erythropoietin (rHuEPO) for 7 d and generated cells that consisted of 30-60% CFU-E, but no BFU-E. A serum-free medium was used that allowed development of the same number of erythroid colonies as serum containing medium, but with a greater percentage of larger colonies. This medium consisted of delipidated crystalline bovine serum albumin, iron saturated transferrin, lipid suspension, fibrinogen, thrombin, Iscove's modified Dulbecco's medium/F-12[HAM], and insulin plus rHuEPO. When CFU-E were cultured in a limiting dilution assay and the percentage of nonresponder wells was plotted against cell concentration, both serum-free cultures and serum-containing cultures yielded overlapping straight lines through the origin indicating that CFU-E development did not depend on accessory cells and that insulin acted directly on the CFU-E. Human recombinant interleukin 3 (IL-3) and/or granulocyte-macrophage colony-stimulating factor had no effect on CFU-E growth, while they markedly enhanced BFU-E growth. Physiological concentrations of recombinant human insulin-like growth factor I (IGF-I) enhanced CFU-E growth in the absence of insulin and, together with rHuEPO in serum-free medium, provided a plating efficiency equal to that of serum-containing medium. Limiting dilution analysis in serum-free medium with IGF-I showed a straight line through the origin indicating that IGF-I also acted directly on the CFU-E and not through an effect on accessory cells. These data demonstrate that CFU-E do not require accessory cells, but do require IGF-I and/or insulin which act directly on the CFU-E.
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PMID:Human colony-forming units-erythroid do not require accessory cells, but do require direct interaction with insulin-like growth factor I and/or insulin for erythroid development. 265 78

We evaluated the biologic effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in 25 patients with malignancy and/or bone marrow failure of diverse etiologies. The continuous infusion of GM-CSF (15 to 500 micrograms/m2/day) elicited marked leukocytosis (2- to 70-fold increase), consisting primarily of neutrophils, eosinophils, and monocytes. Six patients with cytopenias experienced a multilineage response characterized by significant increases in platelet counts and improvement in erythropoiesis. Response in blood counts was accompanied by significant increases in bone marrow cellularity, myeloid:erythroid cell ratios, and frequency of cycling progenitors, indicating an effect at the stem cell level. By premature chromosome condensation analysis, neutrophils from patients with myeloid diseases were found to be derived from normal as well as abnormal clones. Side effects were generally mild and commonly included constitutional symptoms and bone pain. These results indicate that GM-CSF is a significant stimulus for hematopoiesis in vivo and might play an important role in several clinical arenas.
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PMID:In vivo biologic activities of recombinant human granulocyte-macrophage colony-stimulating factor. 266 Jun 75

We have established a novel cell line, designated as TF-1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte-macrophage colony-stimulating factor (GM-CSF) or on interleukin-3 (IL-3) and carried a homogeneous chromosomal abnormality (54X). Erythropoietin (EPO) also sustained the short-term growth of TF-1, but did not induce erythroid differentiation. These three hematopoietic growth factors acted on TF-1 synergistically. Transforming growth factor-beta and interferons inhibited the factor-dependent growth of TF-1 cells in a dose-dependent fashion, and monocyte-colony stimulating factor and interkeukin-1 enhanced the GM-CSF-dependent growth of TF-1. Ultrastructural studies revealed some very immature features in this cell line. Although TF-1 cells do not express glycophorin A or carbonyl anhydrase I, the morphological and cytochemical features, and the constitutive expression of globin genes, indicate the commitment of TF-1 to erythroid lineage. When induced to differentiate, TF-1 entered two different pathways. Specifically, hemin and delta-aminolevulinic acid induced hemoglobin synthesis, whereas TPA induced dramatic differentiation of TF-1 into macrophage-like cells. In summary, TF-1 is a cell line of immature erythroid origin that requires GM-CSF, IL-3, or EPO for its growth and that has the ability to undergo differentiation into either more mature erythroid cells or into macrophage-like cells. TF-1 is a useful tool for analyzing the human receptors for IL-3, GM-CSF, and EPO or the signal transduction of these hemopoietic growth factors.
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PMID:Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. 266 85


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