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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 effects of several growth factors on the proliferation of fibroblastic colony-forming units (CFU-F) were studied. In the present study CFU-F colonies were found to consist of fibroblasts, macrophages, and endothelial cells. Growth factors, including interleukin 3 (IL-3), interleukin 1 alpha (IL-1 alpha), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and buffalo rat liver cell-conditioned medium (BRL-CM) were tested for stimulation of the proliferation of CFU-F in a standard culture in both 2% and 15% serum. Overall, the colony numbers produced in 15% serum were much higher than in 2% serum with or without growth factors. However, the influence of several growth factors on CFU-F cultured in 2% serum was relatively greater than in 15% serum when compared to controls. The stimulation of CFU-F by FGF only occurred in culture with 15% serum, and the stimulation by PDGF only occurred with 2% serum. Overall, the strongest stimulations were produced by PDGF, IL-3, and BRL-CM. Combining the other growth factors with IL-3, PDGF, or IL-1 alpha enhanced their effects only modestly. The stimulation by growth factors included increases of the cell numbers between and within colonies as well as an increase in the number of colonies. The study produced results that suggest a complex interaction mediated by growth factors between fibroblasts and other stromal cells within the CFU-F colonies and within the bone marrow itself.
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PMID:Dissecting the hematopoietic microenvironment. VI. The effects of several growth factors on the in vitro growth of murine bone marrow CFU-F. 232 69

Purified normal murine bone marrow-derived fibroblasts were shown to produce a factor that stimulates the in vitro growth of fibroblastic colony-forming unit (CFU-F) colonies. Conditioned medium from the purified fibroblasts (F-CM) also stimulated pure marrow fibroblasts themselves. Analysis of the F-CM detected the presence of macrophage colony-stimulating factor (M-CSF), and low levels of interleukin 1 (IL-1) and interleukin 6 (IL-6), but no detectable levels of interleukin 3 (IL-3), interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Macrophages and endothelial cells, freed from other bone marrow components, required the F-CM if no other growth factors were added. We conclude that F-CM contains an autocrine factor, which the evidence suggests is IL-1, for bone marrow fibroblasts, and a paracrine factor (CSF-1) for macrophages and/or endothelial cells.
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PMID:Dissecting the hematopoietic microenvironment. VII. The production of an autostimulatory factor as well as a CSF by unstimulated murine marrow fibroblasts. 232 70

Highly purified murine granulocyte-macrophage progenitor cells (CFU-GM) were used as target cells to assess the possible direct effects of purified preparations of recombinant murine gamma-interferon, prostaglandin E, recombinant human heavy chain (acidic) ferritin, and recombinant human tumor necrosis factor alpha (TNF-alpha) on progenitor cells in vitro. Target CFU-GM, with cloning efficiencies of up to 84% and containing 0-3% morphologically recognizable accessory cells at the initiation of the culture period, were plated at a density of 100-150 cells/dish in the presence or absence of pure suppressor molecules. Colony formation was stimulated with either crude pokeweed mitogen-stimulated mouse spleen conditioned medium, pure natural murine macrophage colony-stimulating factor, or pure recombinant murine granulocyte-macrophage colony-stimulating factor. All four suppressor molecules were active in vitro against purified CFU-GM as assessed by their ability to inhibit colony or cluster formation. No apparent difference in the degree of responsiveness to prostaglandin E, gamma-interferon, or human heavy chain (acidic) ferritin was noted in the presence of pokeweed mitogen-stimulated mouse spleen conditioned medium, granulocyte-macrophage colony-stimulating factor, or macrophage colony-stimulating factor. In contrast, TNF-alpha in cultures containing macrophage colony-stimulating factor slightly, but significantly, potentiated colony formation. TNF-alpha also appeared more active at suppressing colony formation at lower concentrations in pokeweed mitogen-stimulated mouse spleen conditioned medium than in granulocyte-macrophage colony-stimulating factor-stimulated cultures of purified CFU-GM. The results suggest that TNF-alpha, human heavy chain (acidic) ferritin, gamma-interferon, and prostaglandin E can act directly at the progenitor cell level.
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PMID:Effects of hematopoietic suppressor molecules on the in vitro proliferation of purified murine granulocyte-macrophage progenitor cells. 244 53

The effect of a number of purified or recombinant hematopoietic growth factors, including recombinant erythropoietin (rEpo), thrombocytopoiesis stimulating factor (TSF), recombinant interleukin 1 alpha (rIL-1 alpha), recombinant granulocyte colony-stimulating factor (rG-CSF), macrophage colony-stimulating factor (CSF-1), recombinant interleukin 3 (rIL-3), and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on megakaryocyte (MK) colony formation by normal human marrow cells in a serum-depleted assay system was determined. Neither rEpo, TSF, CSF-1, rIL-1 alpha, nor rG-CSF alone augmented MK colony formation. Both rGM-CSF and rIL-3 at optimal doses increased MK colony formation eightfold and tenfold, respectively, above baseline values. Addition of increasing amounts of either rGM-CSF or rIL-3 led to progressively greater numbers of MK colonies formed until plateau levels were reached. Both rGM-CSF and rIL-3 also led to a dose-related increase in the number of cells per MK colony formed in culture. These molecules were equivalent stimulators of MK colony formation when their effects at optimal concentrations were compared. The effects of rGM-CSF and rIL-3 were additive at suboptimal concentrations of rIL-3 in that colony formation by a combination of the two growth factors approximated the sum of colony formation by each growth factor alone. These data suggest that rGM-CSF and rIL-3 alone and in combination are important regulators of in vitro megakaryocytopoiesis at the progenitor cell level.
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PMID:Effect of recombinant and purified hematopoietic growth factors on human megakaryocyte colony formation. 245 73

We have investigated the proliferative effects of several combinations of hematopoietic growth factors in agar cultures of murine bone marrow cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) synergized with granulocyte colony-stimulating factor (G-CSF), while G-CSF also synergized with macrophage colony-stimulating factor (CSF-1) and interleukin 3 (IL3), resulting in colony numbers greater than the sum of the numbers of colonies formed with each factor alone. In addition, these combinations resulted in increased colony sizes, with the formation of day-14 colonies with diameters greater than 0.5 mm. The combination of GM-CSF plus IL3 showed an increase in numbers of colonies that approximated the sum of that seen with each factor alone, however, the size of the colonies was increased with a number of day-14 and day-21 colonies having diameters greater than 0.5 mm. These data add to the list of hematopoietic factors known to synergistically stimulate myeloid progenitors and suggest that some of these interactions may be on early progenitor cells with high proliferative potentials.
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PMID:Synergistic interactions between hematopoietic growth factors as detected by in vitro mouse bone marrow colony formation. 245 75

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
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PMID:A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. 246 30

Recombinant interleukin (IL) 1 beta and tumor necrosis factor/cachectin (TNF-alpha) induce, usually within 2 h, a dose-dependent increase in the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF mRNA in cultured human fibroblasts. Maximal induction is reached at about 4-8 h and usually last for at least 48 h. IL 1 beta and TNF have additive effects on the levels of GM- and G-CSF mRNA, and on the secretion of G-CSF activity into the culture medium. IL 1 alpha has the same additive effect that IL 1 beta has with TNF, but no additive effect with IL 1 beta. In contrast, the high basic level of M-CSF (CSF-1) mRNA shows little or lower variations in response to IL 1, TNF-alpha or both IL 1 and TNF-alpha also induce, with similar kinetics, an increase in IL 1 beta but not mRNA level. In contrast to what is observed with macrophages and endothelial cells, E. coli lipopolysaccharide does not modify the fibroblast CSF mRNA level up to 48 h of culture.
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PMID:Interleukin 1 and tumor necrosis factor-alpha additively increase the levels of granulocyte-macrophage and granulocyte colony-stimulating factor (CSF) mRNA in human fibroblasts. 246 2

In this study we show that bone marrow macrophages (BMM phi), derived by culturing bone marrow stem cells in macrophage colony-stimulating factor (M-CSF)-containing medium, and activated by an optimal dose of interferon-gamma, selectively interacted with only some out of a group of protein antigen-specific T cell clones as measured by antigen-specific T cell proliferation. Antibody inhibition experiments employing monoclonal anti-CD4 antibodies suggest that the failure of various T cell lines to cooperate with BMM phi might be due to a low avidity of the interaction between these T cells and the accessory cells. We further show that BMC that were allowed to mature in the presence of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) developed into highly efficient accessory cells leading to antigen-specific activation of all T cell clones tested. No correlation was found with the level of expression of MHC class II genes induced in GM-CSF-treated BMM phi, although significant amounts of transcripts of A alpha, A beta and of the non MHC-encoded invariant gamma-chain were detected by Northern blot analysis.
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PMID:Induction of antigen presentation capacity and MHC class II gene expression in bone marrow macrophages derived from GM-CSF-supplemented in vitro cultures. 246 53

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous signals, preferentially provided by the T cell-derived lymphokine GM-CSF. Stimulation of hematopoiesis and amplification of defense mechanisms after T cell activation thus might involve not only monocytes but also PMN, a cell type previously believed to be biosynthetically inactive.
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PMID:Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes. 1456 12

Five glycoprotein growth factors capable of stimulating the proliferation and differentiation of haemopoietic progenitor cells in vitro have been identified and sequenced over the past ten years. Recombinant DNA technology has recently enabled the production of sufficient amounts of these agents for preclinical testing. Erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) have already entered clinical studies in humans. Interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF) should soon be available for use in humans. EPO corrects the anaemia of end stage renal failure, improving the quality of life for such patients and preventing the need for red cell transfusions. At high dose it increases platelet production in vitro and in vivo and may be of value in humans to prevent the thrombocytopaenia associated with chemotherapy. G-CSF and GM-CSF have been used in several clinical studies. Administration of both growth factors results in a leucocytosis, G-CSF predominantly increasing neutrophil production and GM-CSF increasing production of neutrophils, eosinophils and monocytes. The optimal administration of these agents is via continuous intravenous infusion or daily subcutaneous injections at doses of 3-10 micrograms/kg/24 h. GM-CSF has shown promising results in patients with AIDS and the myelodysplastic syndrome and both G-CSF and GM-CSF have reduced the duration of neutropaenia and incidence of infection associated with chemotherapy. These agents may allow an escalation of the dose-intensity of chemotherapy in the future and thereby, hopefully, increase the response rate and survival for patients with a variety of neoplasms. Several other potential roles for these haemopoietic growth factors are discussed.
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PMID:Clinical trials with haemopoietic growth factors. 249 Dec 51


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