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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)

Hematopoetic growth factors stimulate the proliferation of leukocyte precursors in bone marrow cultures, but some also augment the responsiveness of mature effector cells. For example, granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances superoxide production and cytotoxicity of neutrophils stimulated by diverse agonists. We show that preexposure of neutrophils to GM-CSF is absolutely required for the induction of leukotriene B4 and platelet-activating factor (PAF) synthesis by a soluble agonist, C5a or N-formyl-methionyl-leucine-phenylalanine (FMLP). Lipid mediator synthesis occurs very rapidly after triggering with the second signal, and under identical conditions superoxide release is enhanced. Interleukin-3 (IL-3), another hematopoetic growth factor, enhances granule release and more profoundly leukotriene C4 (LTC4) synthesis in basophils stimulated by immunoglobulin-E (IgE)-dependent or -independent agonists. Sequential stimulation with IL-3 and C5a results in the production of large quantities of LTC4, while neither factor alone induces the release of lipid mediators. We conclude that a major function of these cytokines is to allow lipid mediator synthesis in effector cells after triggering with agonists which by themselves do not induce the production of bioactive lipids. We also propose that lipoxygenase metabolites and PAF represent an autocrine response amplification pathway in effector cells which might explain the enhanced responsiveness of cells primed by these cytokines.
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PMID:Growth factors, lipid mediators and effector cells. 196 12

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic hematopoietic growth factor that induces both growth and differentiation of tissue macrophages. The subcellular mechanism of action of GM-CSF is unknown. We have examined the effect of GM-CSF on the immediate early response gene, Egr-1, in murine peritoneal macrophages. Our data demonstrate that recombinant GM-CSF (25 units/ml) produces a 12-fold increase in Egr-1 mRNA within 30 min. Pretreatment with cycloheximide (10 micrograms/ml) had no effect on the ability of GM-CSF to increase Egr-1 mRNA. In nuclear runoff studies, GM-CSF increased the transcription rate of Egr-1 by 10-fold at 10 min. The maximal effect on Egr-1 transcription occurred at 25 min (13-fold) and decreased by 45 min. The half-life of Egr-1 mRNA in GM-CSF-treated macrophages is 13-21 min. We were unable to calculate the half-life in control cells, however, because of the short half-life and low level of constitutive expression of Egr-1 mRNA. Endogenous protein kinase C activity in macrophages was depleted by treatment with 12-O-tetradecanoylphorbol-13-acetate for 24 h. GM-CSF increased Egr-1 mRNA in protein kinase C-depleted macrophages, whereas the stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate on Egr-1 was blocked. These data show that GM-CSF rapidly increases transcription of Egr-1 mRNA. The effect of GM-CSF on Egr-1 mRNA does not require de novo protein synthesis or protein kinase C. These findings provide a basis for investigating the molecular mechanism of action of GM-CSF in tissue macrophages.
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PMID:Granulocyte-macrophage colony-stimulating factor induces transcriptional activation of Egr-1 in murine peritoneal macrophages. 200 29

In the present study, culture supernatants from larger granular lymphocytes (LGL) that were activated with Candida albicans antigens were shown to stimulate the ability of neutrophils to inhibit fungal growth. Identification of the activation factors showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was involved. Human peripheral blood mononuclear cells were fractionated by Percoll density centrifugation and each subpopulation of cells was stimulated with C albicans yeast cells. GM-CSF was produced in those fractions enriched for LGL, but not T lymphocytes or adherent monocytes. Additionally, the phenotype of the GM-CSF-producing cell was found to be CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies demonstrated that GM-CSF appeared in the supernatants within 2 days of culture and continued to be produced up to 7 days. Optimal stimulation of LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL. Thus, LGL play an important role in host defense against this opportunistic pathogen by producing cytokines, including GM-CSF, which in turn activates the fungicidal activity of neutrophils.
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PMID:Production of granulocyte-macrophage colony-stimulating factor by large granular lymphocytes stimulated with Candida albicans: role in activation of human neutrophil function. 202 83

This study reports the detection of an activity that stimulates the development of a subclass of burst-forming unit-erythroid (BFU-E) progenitors giving rise to small bursts in semi-solid cultures established in the presence of saturating concentrations of erythropoietin. These progenitors are considered to be mature BFU-E. The activity is found in extracts from kidney cells and appears to be physiologically regulated as it was respectively enhanced and decreased in kidneys from anemic and polycythemic mice. The disappearance of activity in kidney-cell extracts during long-term polycythemia correlated with an accumulation of mature BFU-E in the spleen and bone marrow of polycythemic mice. Using specific neutralizing antibodies and in vitro tests, we also show that this activity is different from hemopoietins known to share burst promoting activity (Interleukin-3 [IL-3], granulocyte-macrophage colony-stimulating factor [GM-CSF], Interleukin-4 [IL-4], erythropoietin [EPO], human interleukin for DA cells [HILDA]) and that it can stimulate erythroid differentiation in long term bone marrow cell cultures.
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PMID:Kidney cell lysates contain an activity that stimulates mature erythroid burst-forming-unit (mBFU-E) proliferation. 212 18

The expression of two cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3), has been investigated in MLA-144 cells before and after induction with phorbol 12-myristate 13-acetate. We describe an adaptation of the polymerase chain reaction (PCR) for highly accurate quantitation of mRNA or DNA from a small number of cells. Aliquots of the PCR mixture containing cDNA copies of the RNA to be assayed were added to serial dilutions of a competitor DNA fragment that differed from the cDNA of interest by having either a small intron or a mutated internal restriction enzyme site. Therefore, the same primers were used to coamplify the unknown and the competitor. The ratio of products remains constant through the amplification and can be readily quantitated. In unstimulated cells, no GM-CSF or IL-3 mRNA could be detected. However, with appropriate induction, mRNA for both cytokines was detected and quantitated in as few as 200 cells. Competitive PCR was also used to accurately quantitate the copy number of the human GM-CSF gene in normal human cells, in a clonal population of cells from a patient with 5q- syndrome, and in a human-hamster cell line known to have only one copy of the human GM-CSF gene.
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PMID:Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. 218 47

We investigated the production of interleukin-3 (IL-3)-like factor by murine astrocytes. Supernatants from lipopolysaccharide (LPS)-stimulated astrocytes induced proliferation of IC-2, an IL-3- and granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent cell line. This activity was completely neutralized by the antibody against GM-CSF but not by the anti-IL-3 monoclonal antibody. Northern blot analysis revealed the expression of GM-CSF mRNA, but not of IL-3 mRNA, in cultured astrocytes. These results indicate that with proper stimuli murine astrocytes produce GM-CSF.
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PMID:Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes. 219 11

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

The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5'-flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells.
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PMID:The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity. 223 34

In this report, the biological properties of human recombinant interleukin-3 (rhIL-3) were studied. We investigated the range of unfractionated, purified and single cell human progenitors responsive to IL-3; compared the colony types observed with those obtained in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). The results show that IL-3 directly stimulates the formation of colonies derived from eosinophil and, to a lesser degree, granulocyte and macrophage progenitors. In combination with erythropoietin, it supports the development of erythroid and mixed-erythroid colonies. Furthermore, the data show that IL-3 is a more potent stimulus for both erythroid and eosinophil progenitors than GM-CSF. Interleukin-3 stimulates the formation of both compact and dispersed colonies derived from eosinophil progenitors, whereas GM-CSF stimulates the formation of only the compact type. We conclude that some of the proliferative effects of IL-3 observed on unfractionated and semipurified bone marrow populations are indirect and most likely involve accessory cell interactions.
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PMID:Proliferative properties of unfractionated, purified, and single cell human progenitor populations stimulated by recombinant human interleukin-3. 229 98

Although the genes for four hematopoietic colony-stimulating factors (CSFs) have been cloned, neither the mechanism of the regulation of their production nor their cellular origins have been established with certainty. Monocytes are known to produce colony-stimulating and burst-promoting activities, as well as several monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). These monokines indirectly stimulate other mesenchymal cells to produce certain colony-stimulating factors such as granulocyte-macrophage CSF (GM-CSF). To determine whether monocytes produce other CSFs and if so, to compare the mechanism of regulation of production with that of endothelial cells and fibroblasts, we investigated the synthesis of CSFs by monocytes, human umbilical vein endothelial cells, and fibroblasts. We used total cellular RNA blot analysis to determine interleukin-3 (IL-3), GM-CSF, granulocyte CSF (G-CSF), and monocyte CSF (M-CSF) messenger RNA (mRNA) content and immunoprecipitation or bioassay to confirm the presence of the specific secreted proteins. The results indicate that M-CSF mRNA and protein are produced constitutively by all three cell types and their level of expression does not increase after induction. In contrast, GM-CSF and G-CSF mRNAs are barely detectable in uninduced monocytes and show an increase in expression after lipopolysaccharide treatment. Retrovirus-immortalized endothelial cells, unlike primary endothelial cells or both primary and immortalized fibroblasts, produce IL-1 constitutively; this correlates with their constitutive production of GM-CSF and G-CSF. IL-3 mRNA was not detectable in any of these cells either before or after induction. The results indicate that these mesenchymal cells can produce three CSFs: GM-CSF, G-CSF, and M-CSF; furthermore, the data suggest that the mechanism of regulation of M-CSF production is different from that of GM-CSF and G-CSF, and that the latter two inducible CSFs are regulated by different factors in monocytes compared with the other mesenchymal cells.
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PMID:Interleukin-1, tumor necrosis factor, and the production of colony-stimulating factors by cultured mesenchymal cells. 245 80


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