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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)

We have investigated the role that hemopoietic regulatory molecules may play in mouse embryogenesis prior to the appearance of hemopoietic stem cells or their microenvironments. Using polymerase chain reaction analysis, we detected mRNA transcripts for interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) but not for granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3 in mouse blastocysts at 3.5 days of gestation. Functional IL-6 protein was also detected in cultured blastocysts as a secreted product, as was an activity consistent with the presence of LIF protein. The expression of IL-6 and LIF in blastocysts prior to hemopoiesis suggests that these proteins may regulate the growth and development of trophoblasts or embryonic stem cells.
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PMID:The genes for leukemia inhibitory factor and interleukin-6 are expressed in mouse blastocysts prior to the onset of hemopoiesis. 211 4

30 patients with chemotherapy-related leukopenia (white cells 1.0 x 10(9)/l or lower) and fever (temperature 38.5 degrees C or higher) were treated in a double-blind randomised trial with standard antibiotics and 7 days of intravenously administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 2.8 micrograms/kg per day) or placebo. GM-CSF administration resulted in a faster percentage increase of peripheral neutrophil count after 2 and 3 days of treatment, except in patients treated with ablative chemotherapy and autologous bone-marrow transplantation. However, GM-CSF did not shorten the period of fever or antibiotic administration. No side-effects were observed; in particular tumour necrosis factor alpha and interleukin-6 did not increase in the 5 GM-CSF patients tested. These data suggest that a subgroup of patients with chemotherapy-related leukopenia and fever may benefit from GM-CSF treatment in view of the observed effects on neutrophil count.
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PMID:Efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related leukopenia and fever. 214 17

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) exert multiple effects on the proliferation, differentiation, and function of myeloid lineage cells through their interaction with specific cell-surface receptors. There is a considerable degree of overlap in the biological effects of these two growth factors, but little is known about the mechanisms of postreceptor signal transduction. We have investigated the effects of GM-CSF and IL-3 on protein tyrosine-kinase activity in a human cell line, MO7E, which proliferates in response to either factor. Tyrosine-kinase activity was detected using immunoblotting with a monoclonal antibody (MoAb) specific for phosphotyrosine. GM-CSF and IL-3 were found to induce a nearly identical pattern of protein tyrosine phosphorylation using both one- and two-dimensional gel electrophoresis. Tyrosine phosphorylation of two cytosolic proteins in particular was increased more than 10-fold, a 93-Kd protein (pp93) and a 70-Kd protein (pp70). Tyrosine phosphorylation of pp93 and pp70 was observed within 1 minute, reached a maximum at 5 to 15 minutes, and gradually decreased thereafter. Other proteins of 150, 125, 63, 55, 42, and 36 Kd were also phosphorylated on tyrosine in response to both GM-CSF and IL-3, although to a lesser degree. Tyrosine phosphorylation was dependent on the concentration of GM-CSF over the range of 0.1 to 10 ng/mL and on IL-3 over the range of 1 to 30 ng/mL. Stimulation of MO7E cells with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) or cytokines such as G-CSF, M-CSF, interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma, tumor necrosis factor (TNF), or transforming growth factor-beta (TGF-beta) did not induce tyrosine phosphorylation of pp93 or pp70, suggesting that these two phosphoproteins are specific for GM-CSF-or IL-3-induced activation. The extent and duration of phosphorylation of all the substrates were increased by pretreatment of cells with vanadate, an inhibitor of protein-tyrosine phosphatases. Importantly, culture of MO7E cells with vanadate (up to 10 mumol/L) resulted in a dose-dependent increase in GM-CSF-or IL-3-induced proliferation of up to 1.8-fold. These results suggest that tyrosine phosphorylation may be important for GM-CSF and IL-3 receptor-mediated signal transduction and that cell proliferation may be, at least partially, regulated by a balance between CSF-induced protein-tyrosine kinase activity and protein-tyrosine phosphatase activity.
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PMID:Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. 216 6

The study of monocyte/macrophage functions after human immunodeficiency virus type 1 (HIV-1) infection may help in understanding the pathogenesis of AIDS. The production of four cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF), by peripheral blood monocytes/macrophages was evaluated after in vitro infection with HIV-1. HIV-1 infection of these monocytes/macrophages did not result in release of any of these cytokines. Similarly, treatment of uninfected cells with purified recombinant HIV-1 envelope protein did not result in cytokine production. After stimulation with endotoxin or endotoxin plus interferon-gamma, HIV-1-infected monocytes/macrophages produced amounts of TNF alpha, IL-6, GM-CSF, and IL-1 beta comparable to that of uninfected cells. HIV-1 infection does not appear to induce or alter cytokine production by mononuclear phagocytes, which retain the capacity to produce these cytokines after endotoxin stimulation.
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PMID:Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). 218 29

The AF1-19T rat cell line has been found to produce an activity that acts synergistically with colony-stimulating factor 1 (CSF-1) to stimulate primitive high proliferative potential colony-forming cells (HPP-CFC) in mouse bone marrow (BM) that appear to be the same as those stimulated by the combination of 5637-cell-conditioned medium (CM) plus CSF-1 or recombinant human (rh) interleukin 1 (IL-1) plus recombinant murine (rm) interleukin 3 (IL-3) plus CSF-1. AF1-19T also produced granulocyte-macrophage colony-stimulating factor (GM-CSF), which could be separated from this synergistic activity by gel filtration followed by hydroxylapatite chromatography. Results obtained from the mouse thymocyte costimulation assay for IL-1, the hybridoma growth factor assay for interleukin 6 (IL-6), the ability to stimulate HPP-CFC, and the ability to block this stimulation with an antibody to murine IL-1 alpha suggest that the synergistic activity in AF1-19T-CM is probably a mixture of IL-1 activity and IL-6 or an IL-6-like activity. Other workers have described a progenitor cell population in mouse BM (CFU-A) that forms large colonies in response to AF1-19T-CM plus CSF-1 or GM-CSF plus CSF-1. Experiments involving the kinetics of recovery after 5-fluorouracil treatment and generation of progenitors suggest that the GM-CSF-plus-CSF-1-responsive progenitors, and hence CFU-A, are a more mature cell type than the more primitive HPP-CFC, responsive to 5637-cell-CM plus CSF-1 or rhIL-1 plus rmIL-3 plus CSF-1.
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PMID:Progenitor cells in murine bone marrow stimulated by growth factors produced by the AF1-19T rat cell line. 218 22

Proliferation of acute myelogenous leukemia (AML) derived blast cells requires the presence in culture of one or more growth factors. In the majority of cases Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate clonogenicity of AML blasts, which can be synergised by Interleukin-6 (IL-6), Interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). In contrast, macrophage colony-stimulating factor (M-CSF) favors deterministic divisions. A substantial part of AML samples have clonogenic cells which, however, proliferate autonomously in vitro. The production by leukemic cells of a variety of growth or synergizing factors including GM-CSF, G-CSF, IL-1, IL-6, and Tumor Necrosis Factor (TNF) has been demonstrated and a fraction of cases will use these molecules to support clonogenic growth in an autocrine or paracrine fashion. However, unlike the situation with retrovirus-induced murine or avian leukemias, the role of production of CSFs and other cytokines by human leukemic cells in the transformational process remains uncertain.
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PMID:Control of blast cell proliferation and differentiation in acute myelogenous leukemia by soluble polypeptide growth factors. 220 37

Induction of differentiation to macrophages in two different clones of myeloid leukemic cells by the hematopoietic regulatory proteins interleukin-6 (IL-6), or by granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), is shown to be associated with sustained accumulation of c-jun, jun-B, and c-fos mRNA that code for proteins that form complexes that are transcription factors (AP-1). In one but not in the other of these leukemic clones, differentiation is also associated with sustained accumulation of mRNA for the putative transcription factor zif/268. The results indicate that differentiation of myeloid cells by normal hematopoietic regulatory proteins is associated with induction of sustained elevated levels of mRNA for transcription factors that can regulate and maintain gene expression in the differentiation program, and that zif/268 gene expression is not essential for differentiation to macrophages.
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PMID:Induction of genes for transcription factors by normal hematopoietic regulatory proteins in the differentiation of myeloid leukemic cells. 224 2

The immunological and biochemical characteristics of murine megakaryocyte potentiator from lung and bone marrow were examined and compared with thrombopoietic stimulatory factor. Biological activity was not neutralized by anti-erythropoietin, but megakaryocyte potentiator activity from all three sources was abolished or reduced when the preparations were treated with anti-thrombopoietic stimulatory factor or anti-interleukin-6. Megakaryocyte potentiator levels in lung conditioned medium were not found to be enhanced from mice treated with lipopolysaccharide, in contrast to granulocyte-macrophage colony-stimulating factor (GM-CSF) levels. The biochemical properties of murine megakaryocyte potentiator from lung and bone marrow were compared and found to be similar in the elution profiles from anion exchange, gel filtration and reversed phase liquid chromatography. It is concluded that the activities in lung and bone marrow are very similar if not identical, to interleukin-6.
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PMID:Tissue sources of murine megakaryocyte potentiator: biochemical and immunological studies. 238 66

There are different types of myeloid leukemic cells that can be induced to differentiate to mature granulocytes or macrophages by different hematopoietic regulatory proteins. One type of leukemic clone can be induced to differentiate by recombinant macrophage and granulocyte differentiation-inducing protein-type 2 (MGI-2), which we have shown is Interleukin-6 (IL-6), and another type of leukemic clone can be differentiated by recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3. There was no subpopulation of growth factor-responsive or differentiation-defective cells before induction of differentiation in either type of clone. In both clones, induction of differentiation-induced requirement for a hematopoietic protein for cell viability. Viability of the cells was maintained by IL-6, IL-3, or macrophage colony-stimulating factor (M-CSF) but not by GM-CSF in the cells differentiated by IL-6, and by GM-CSF or IL-3 but not by IL-6 or M-CSF in the cells differentiated by GM-CSF or IL-3. The viable cells with a differentiated phenotype continued to multiply. In undifferentiated leukemic cells with no or few surface receptors for some of these proteins, there was an upregulation of the number of receptors during differentiation for the proteins to which the cells responded. But there were also differentiating leukemic cells with an upregulation of GM-CSF receptors although GM-CSF could not maintain the viability of the differentiating cells. The results indicate that induction of hormone responsiveness and upregulation of the hormone receptors can both occur in differentiating leukemic cells, and that the regulation of these two events can be separated.
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PMID:Induction of dependence on hematopoietic proteins for viability and receptor upregulation in differentiating myeloid leukemic cells. 254 28

Two cDNA clones encoding a receptor for human granulocyte-macrophage colony-stimulating factor (hGM-CSF-R) were isolated by expression screening of a library made from human placental mRNA. Pools of recombinant plasmid DNA were electroporated into COS cells which were then screened for their capacity to bind radioiodinated hGM-CSF using a sensitive microscopic autoradiographic approach. The cloned GM-CSF-R precursor is a 400 amino acid polypeptide (Mr 45,000) with a single transmembrane domain, a glycosylated extracellular domain and a short (54 amino acids) intracytoplasmic tail. It does not contain a tyrosine kinase domain nor show homology with members of the immunoglobulin super gene family, but does show some significant sequence homologies with receptors for several other haemopoietic growth factors, including those for interleukin-6, erythropoietin and interleukin-2 (beta-chain) and also to the prolactin receptor. When transfected into COS cells the cloned cDNA directed the expression of a GM-CSF-R showing a single class of affinity (KD = 2(-8) nM) and specificity for human GM-CSF but not interleukin-3. Messenger RNA coding for this receptor was detected in a variety of haemopoietic cells known to display hGM-CSF binding, and cross-linking experiments revealed a similar size for the glycosylated receptors in transfected COS and haemopoietic cells.
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PMID:Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. 255 71


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