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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)

Tumor-associated macrophages (TAM) represent a population of tissue macrophages with peculiar biological, biochemical and phenotypic properties. Here we have briefly analyzed two different mechanisms involved in the regulation of the levels of TAM: the production of tumor-derived chemotactic factors for mononuclear phagocytes and in situ proliferation of TAM. Two clones selected from the murine sarcoma line B77 showed a different capacity to produce the tumor-derived chemotactic factor known as JE. Studies with these clones demonstrated a correlation between in vitro production of the protein JE, expression of JE mRNA and macrophage content in tumor tissues, suggesting that the production of chemotactic factors can play a role in the regulation of TAM accumulation. Moreover, it has been shown that TAM had high levels of proliferative activity compared to peritoneal exudate macrophages. In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, the expression of c-fms and macrophage-colony-stimulating factor (M-CSF) was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts, while sarcoma cells had high levels of M-CSF mRNA. Sarcoma-cell-conditioned medium had M-CSF activity on bone marrow cells: this activity was blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M-CSF secreted by sarcoma cells and acting on c-fms-expressing TAM. A better understanding of the regulation and function of TAM may provide a less empirical basis for a rationale design of therapeutic approaches.
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PMID:The role of macrophages in the regulation of primary tumor growth. 188 19

Human promyelocytic leukemia HL-60 cells were induced to differentiate into macrophages by PMA (phorbol 12-myristate-13-acetate), 1-alpha-25-(OH)2D3(1-alpha-25-dihydroxyvitamin D3, hrGM-CSF (human recombinant granulocyte-macrophage colony-stimulating factor) and into granulocytes by DMSO (dimethylsulfoxide). We found that the differentiation of HL-60 cells into macrophages was accompanied by transcription of the c-fms oncogene, which was assessed by a modified PCR (polymerase-chain reaction) method. After treatment with a c-fms anti-sense oligomer, the PMA and hrGM-CSF induced macrophage differentiation of HL-60 cells was significantly inhibited, whereas either 1-alpha-25-(OH)2D3 induced macrophage or DMSO and hrGM-CSF induced granulocytic differentiation was not inhibited. Furthermore, we treated the HL-60 cells with M-CSF (macrophage-colony stimulating factor or CSF-1) anti-sense N degrees 2 (see Figure 1) in the presence of PMA, hrGM-CSF, 1-alpha-25-(OH)2D3 and DMSO. The results showed that this treatment leads to a significant inhibition of PMA and hrGM-CSF-induced macrophage differentiation, but has no influence on the 1-alpha-25-(OH)2D3-induced macrophage differentiation and DMSO-induced granulocytic differentiation. It was further demonstrated that the M-CSF (or CSF-1) and c-fms antisense oligomers acted synergistically on inhibition of macrophage formation induced by PMA and hrGM-CSF, but had no inhibitory effect on the macrophage formation induced by 1-alpha-25-(OH)2D3. Thus we concluded firstly, that HL-60 cells differentiate into macrophages along two different pathways: one is involved in the action of the c-fms oncogene and the other is not. Secondly, an autocrine circuit of M-CSF (or CSF-1) action may exist in the macrophage formation induced by PMA and hrGM-CSF.
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PMID:The role of the c-fms oncogene in the regulation of HL-60 cell differentiation. 214 86

Colony-stimulating factor-1 (CSF-1 or M-CSF) supports the proliferation and survival of mononuclear phagocytes by binding to a receptor (CSF-1R) encoded by the c-fms proto-oncogene. Whereas the CSF-1R kinase is normally regulated by ligand, receptors bearing 'activating mutations' act constitutively as enzymes and can transform fibroblasts and haemopoietic cells of different lineages. Introduction of human CSF-1R enables mouse NIH-3T3 cells to form colonies in agar in response to human CSF-1 and to proliferate in serum-free medium supplemented with CSF-1, albumin, transferrin and insulin. Similarly, expression of human CSF-1R in interleukin 3-dependent mouse FDC-P1 myeloid cells enables them to grow in CSF-1. High levels of CSF-1R expression in FDC-P1 cells can induce factor-independent growth which is abrogated by a 'neutralizing' monoclonal antibody to the receptor. Therefore, critical mutations in the c-fms gene or overexpression of CSF-1R in immature myeloid precursors might each contribute to leukaemia.
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PMID:Signal-response coupling mediated by the transduced colony-stimulating factor-1 receptor and its oncogenic fms variants in naive cells. 215 60

Colony-stimulating factor-1 (CSF-1 or M-CSF) regulates pleiotropic developmental and functional responses of macrophages and their committed bone marrow progenitors and supports the viability of cells of the mononuclear phagocyte lineage. Its actions are mediated through its binding to cell surface CSF-1 receptors (CSF-1R) that exhibit ligand-stimulated tyrosine kinase activity. CSF-1R-induced phosphorylation of intracellular protein substrates initiates a cascade of biochemical reactions that relay signals to the cell nucleus, elicit transcription of CSF-1-responsive genes and culminate in cell division. The actions of the CSF-1R kinase can be interrupted by binding of certain monoclonal antibodies to the extracellular domain of the receptor or by agents which activate protein kinase C and accelerate receptor turnover. CSF-1R is encoded by the c-fms proto-oncogene, and specific genetic alterations, which constitutively activate the receptor kinase, provide sustained signals for cell growth leading to cell transformation. Perturbations in the structure or expression of the c-fms proto-oncogene might therefore contribute to leukemia.
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PMID:Regulation of mononuclear phagocyte proliferation by colony-stimulating factor-1. 215 78

Colony-stimulating factor 1 (CSF-1) is required for the survival, proliferation and differentiation of monocytes. We previously demonstrated that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein and that the induction of Na+ influx by CSF-1 is a pertussis toxin-sensitive event. The present studies have examined activation of protein kinase C as a potential intracellular signaling event induced by the activated CSF-1 receptor. The results demonstrate that CSF-1 stimulates translocation of protein kinase C activity from the cytosol to membrane fractions. This activation of protein kinase C was sensitive to pretreatment of the monocytes with pertussis toxin. Lipid distribution studies demonstrated that phosphatidylcholine (PC) is the major phospholipid in human monocytes. Moreover, the results indicate that CSF-1 stimulation is associated with decreases in PC, but not in phosphatidylinositol (PI), levels. The absence of an effect of CSF-1 on PI turnover was confirmed by the lack of changes in inositol phosphate production. In contrast, CSF-1 stimulation was associated with increased hydrolysis of PC to phosphorylcholine and diacylglycerol (DAG) in both intact monocytes and cell-free assays. Furthermore, the increase in PC turnover induced by CSF-1 was sensitive to pertussis toxin. The results also demonstrate that the induction of Na+ influx by CSF-1 is inhibited by the protein kinase C inhibitors staurosporine and the isoquinoline derivative H7, but not by HA1004.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factor 1 activates protein kinase C in human monocytes. 219 73

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.
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PMID:Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin. 238 56

Colony-stimulating factor 1 (CSF-1) selectively supports the survival, proliferation, and maturation of hemopoietic cells of the monocyte/macrophage lineage. Although the cellular receptor for CSF-1, (the c-fms protein) is a protein-tyrosine kinase activated by the binding of CFS-1, the role of phosphorylation of cellular proteins in CSF-1 signal transduction is poorly understood. Therefore, we examined the CSF-1-stimulated phosphorylation of cellular proteins in human BeWo choriocarcinoma cell line (known to express the c-fms protein). BeWo cells were metabolically labeled with 32Pi, stimulated with recombinant human CSF-1, and extracted with detergent. Phosphotyrosyl proteins were isolated from detergent extracts by affinity chromatography on a highly specific antibody to phosphotyrosine. Rapid phosphorylation of 170-kd protein, followed closely by the phosphorylation of a 56-kd protein, was observed in response to CSF-1. The 170-kd phosphotyrosyl protein bound to wheat germ agglutinin and was secondarily immunoprecipitated with a specific anti-fms serum, consistent with its identity as the CSF-1 receptor. Although purified human macrophages that proliferate in culture in response to CSF-1 are not generally accessible, CSF-1 did stimulate the phosphorylation of a 56-kd protein in intact mononuclear leukocytes from human peripheral blood. Thus, the BeWo cell line may represent a good model for the study of CSF-1-stimulated cellular protein phosphorylation.
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PMID:Identification of tyrosine-phosphorylated colony-stimulating factor 1 (CSF-1) receptor and a 56-kilodalton protein phosphorylated in intact human cells in response to CSF-1. 246 91

Colony-stimulating factor 1 (CSF-1) regulates the survival, growth, and differentiation of monocytes through binding to a single class of high affinity receptors. The present studies demonstrate that the interaction of CSF-1 with monocyte membranes is associated with a 2.4-fold increase in specific binding of the GTP analogue, GTP gamma S. Scatchard analysis of the GTP gamma S binding data indicated that CSF-1 stimulates GTP binding by increasing the affinity, rather than the number, of available sites. This stimulation of GTP binding by CSF-1 was also associated with an increase in GTPase activity. Furthermore, the CSF-1-induced stimulation of GTPase activity was sensitive to pertussis toxin. We also demonstrate that CSF-1 stimulates Na+ influx into monocytes by an amiloride-sensitive mechanism, presumably the Na+/H+ antiport. This CSF-1-stimulated influx of Na+ was further associated with an increase in Na+,K+-ATPase activity. Moreover, this stimulation of Na+ influx and Na+,K+-ATPase activity by CSF-1 was sensitive to pertussis toxin. Finally, we demonstrate that CSF-1-induced proliferation is also a pertussis toxin-sensitive event. The present findings thus suggest: 1) that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein; and 2) that a pertussis toxin-sensitive G protein is involved in the induction of Na+ influx by CSF-1.
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PMID:Colony-stimulating factor 1-induced Na+ influx into human monocytes involves activation of a pertussis toxin-sensitive GTP-binding protein. 284 56

Colony-stimulating factor 1 (CSF-1) is a glycoprotein growth factor that specifically regulates the survival, proliferation and differentiation of mononuclear phagocytes and their precursors via a cell surface receptor selectively expressed on these cell types. The purified receptor is a single glycosylated polypeptide, Mr 165 000, which exhibits CSF-1-dependent autophosphorylation in tyrosine. CSF-1 alone regulates cells of the mononuclear phagocytic series (CSF-1-dependent colony-forming unit [CFU-C]----monoblast----promonocyte----monocyte----macrophage). However, the presence of a multipotent haemopoietic cell growth factor, haemopoietin-1, permits CSF-1 to stimulate precursors of CFU-C to proliferate and differentiate to macrophages. Precursors of CFU-C possess low levels of the CSF-1 receptor but there is an increase in receptor levels on CFU-C just before their differentiation to adherent, proliferating mononuclear phagocytes. As the timing of this developmentally associated increase in receptor expression coincides with the acquisition of responsiveness to CSF-1 alone, it is an early indicator of determination to the mononuclear phagocytic lineage.
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PMID:Action of the colony-stimulating factor, CSF-1. 301 14

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. The CSF-1 receptor was purified from cell membranes of the J774.2 mouse macrophage cell line by solubilization with Triton X-100, CSF-1 affinity chromatography, and gel filtration. The purified receptor is a protein or glycoprotein of 165 kDa comprising a single polypeptide chain that is not covalently associated, either as a homopolymer, or with any other protein. CSF-1 stimulated autophosphorylation of the purified receptor in tyrosine residues. Casein but not histone was shown to act as a substrate for the tyrosine protein kinase activity of purified receptor.
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PMID:Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity. 302 75


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