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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 examined the ability of two recombinant human cytokines, granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF) and interferon-gamma (rHu-IFN-gamma) to activate antibacterial mechanisms in human pulmonary macrophages (PM) and peripheral blood monocytes (PBM). Growth of Legionella pneumophila (LP) was assessed in PM or PBM which had been exposed to either rHu-IFN-gamma (500-1000 u/ml) or rHu-GM-CSF (1 to 10,000 u/ml). In both PM and PBM exposed to 500 u/ml rHu-IFN-gamma, growth of LP was reduced compared to cells exposed to media alone. By comparison, exposure of these cell types to rHu-GM-CSF had no detectable effect on bacterial replication. In order to investigate potential mechanisms accounting for this observation, the effect of these cytokines on the hydrogen peroxide (H2O2)-releasing capacity of cells was studied. Exposure of PM and PBM to rHu-IFN-gamma (500 to 1000 u/ml) resulted in increased production of H2O2 triggered by phorbol myristate acetate; when subjected to the same experimental conditions, rHu-GM-CSF-exposed cells exhibited no increase in H2O2 production. To further clarify the role of rHu-IFN-gamma-induced augmentation of oxidative metabolism on cellular inhibition of bacterial growth, an amount of catalase capable of completely neutralizing extracellular H2O2 was added to cells before and during infection. This did not abrogate the antibacterial activity of rHu-IFN-gamma. These studies demonstrate that rHu-IFN-gamma but not rHu-GM-CSF is capable of augmenting the capacity of PM and PBM to restrict LP growth. These data suggest that the antibacterial activity of rHu-IFN-gamma in this system may involve oxidative as well as nonoxidative mechanisms.
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PMID:Cytokine activation of antibacterial activity in human pulmonary macrophages: comparison of recombinant interferon-gamma and granulocyte-macrophage colony-stimulating factor. 314 84

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts profound effects on the proliferation, differentiation, and effector function of myeloid lineage cells. In contrast to its growth-promoting effects on normal myeloid progenitor cells, we found that GM-CSF unexpectedly inhibited the colony growth of U937 cells in agar culture. Furthermore, medium conditioned by recombinant GM-CSF(rGM-CSF)-treated U937 cells was found to exert an inhibitory effect on subsequent U937 colony growth that was partially due to the presence of tumor necrosis factor (TNF). By Northern blot analysis, rGM-CSF was shown to induce expression of the TNF gene in U937 cells and in T-lymphocyte-depleted, monocyte-enriched peripheral blood mononuclear cells. Furthermore, rGM-CSF was observed to significantly enhance TNF secretion by monocytes stimulated with endotoxin and phorbol myristate acetate (PMA). These data suggest that some of the biological effects of GM-CSF may be amplified through the release of monokines such as TNF.
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PMID:Human granulocyte-macrophage colony-stimulating factor induces expression of the tumor necrosis factor gene by the U937 cell line and by normal human monocytes. 329

A variety of biologic activities on human hematopoietic stem cells were detected in 12-O-tetradecanoylphorbol-13-acetate-stimulated leukocyte-conditioned medium (TPA-LCM). Partial purification of TPA-LCM demonstrated the presence of human-active granulocyte-macrophage colony-stimulating factor (GM-CSF; Mr 50-70Kd), macrophage-CSF (M-CSF; Mr greater than 100Kd) and possibly a third protein (Mr 24-26Kd) supporting survival and growth of hematopoietic stem cells in vitro. Activities investigated included GM-colony and erythroid burst-potentiation, burst-promoting activity (BPA) and delta granulocyte and delta burst-promoting activities (delta GPA and delta BPA).
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PMID:Human hematopoietic survival and growth factor. 348 87

Two growth factors, interleukin 2 (T cell growth factor) and colony-stimulating factor, are produced concomitantly by a murine EL-4 thymoma cell line after stimulation by phorbol myristate acetate. As shown elsewhere, these thymoma-derived factors appear to be biochemically and functionally indistinguishable from the interleukin 2 and colony-stimulating factor produced by mitogen-stimulated mouse spleen cells. Both factors co-elute during gel filtration with apparent m.w. in the range of 30,000, and both exhibit overlapping isoelectric point profiles between pH 4 and pH 5. Because we were unable to separate these 2 factors by methods based on either m.w. or charge, we have used phenyl-Sepharose chromatography, a method based on hydrophobic interactions, to completely separate murine interleukin 2 and colony-stimulating factor. In contrast with published reports, each of the separated factors exhibits unique biologic activities on lymphocytes and macrophages. Interleukin 2 provides help for antibody synthesis in the nude mouse, but neither enhances interferon production by macrophages nor stimulates macrophage growth. Colony-stimulating factor does not enhance antibody synthesis in the nude mouse but does enhance interferon production by macrophages and stimulate macrophage growth.
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PMID:Biologic properties of chromatographically separated murine thymoma-derived Interleukin 2 and colony-stimulating factor. 617 Jun 82

Interleukin 2 (IL-2) production was studied in a subclone of the murine thymoma EL 4. Phenotypic characterization revealed the EL 4-17-2 line to be Thy-1.2+, Lyt-1.2+, and Lyt-2.2-. Costimulation with 500 ng 12-O-tetradecanoylphorbol 13-acetate (TPA)/ml and 5 micrograms concanavalin A (Con A)/ml induced optimal levels of IL-2. Three related phorbol esters stimulated comparable levels of IL-2 when used in conjunction with Con A. Kinetic experiments indicated that IL-2 first became detectable at 2 hours in TPA-treated cultures, whereas in cultures stimulated with Con A alone IL-2 production was not evident until 8 hours. Flow cytometry indicated that TPA and its related phorbol esters cause a perturbation in the cycling of the cell which may be related to increased IL-2 production. Under the conditions examined, no interferon-gamma (IFN-gamma) was detectable. Conversely, both granulocyte-macrophage colony-stimulating factor (CSF-GM) and interleukin-3 (IL-3) were found under conditions that led to stimulation of IL-2 synthesis. CSF-GM was produced in cultures treated singly with 500 ng TPA/ml or with Con A. IL-3 production was similar to IL-2 production, because optimal levels were found in cultures after combined treatment with phorbol ester and mitogen.
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PMID:Multiple lymphokine production by a phorbol ester-stimulated mouse thymoma: relationship to cell cycle events. 641 58

We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell targets (i.e., K562 cells) spontaneously, but both lyse K562 cells following activation with phorbol myristate acetate. Both adult and newborn PMNs lyse CRBCs and herpes simplex virus-infected CEM cells in antibody-dependent cellular cytotoxicity assays, and this lysis could be enhanced by the cytokines granulocyte-macrophage colony-stimulating factor and gamma interferon. PMN heteroantibody-mediated cytotoxicity, resulting from the use of an antibody with dual specificity to CRBCs and immunoglobulin G FcRII, was greater in newborn PMNs than in adult PMNs; however, monocyte heteroantibody-mediated cytotoxicity, resulting from the use of an antibody to CRBCs and monocyte immunoglobulin G FcRI, was lower in newborn monocytes than in adult monocytes. The percentage, but not the density, of PMNs expressing FcRII was significantly reduced in newborn PMNs compared with that in adult PMNs, while the percentages and densities of FcRI expression were equivalent in newborn and adult monocytes. We conclude that the cytotoxic capability in term newborn PMNs is equivalent to that in adult PMNs, that the activity of newborn PMNs can be enhanced by antibody and/or cytokines, and that PMNs can contribute to the newborn's ability to kill virus-infected cells.
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PMID:Comparison of cytotoxic properties of neonatal and adult neutrophils and monocytes and enhancement by cytokines. 749 73

The effects of normal bone marrow fibroblasts (BM FB) on proliferation and differentiation of 10 myeloid leukemic cell lines were investigated in a serum-free co-culture system. The proliferation of three of the cell lines was supported by BM FB. Three of the myeloid cell lines were inhibited 40-70%. The co-culture supernatants were tested for the secretion of hematopoietic cytokines by bioassays. Except for IL-6, which was already produced constitutively by BM FB, only little amounts of interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) could be detected in several co-culture supernatants. It could be shown that, according to cytologic and functional criteria, the myeloid leukemic cell lines ML-2 and PLB-985 differentiate along the monocyte-macrophage pathway after co-culture with BM FB. They revealed a histiocytic phenotype and could be induced to produce reactive oxygen intermediates (ROI) after stimulation with zymosan or phorbol-myristate-acetate (PMA). Additional proof for differentiation was obtained from flow cytometric analysis of surface differentiation antigens and adhesion molecules. The neutralization of IL-6 activity in the co-cultures by antibodies resulted in prevention of differentiation of PLB-985 cells, while differentiation of ML-2 cells in the co-cultures was not affected by addition of anti-IL-6 antibodies. Furthermore, in co-culture experiments with fibroblasts from skin and foreskin, we found a differentiation of PLB-985 cells comparable to that in co-cultures with BM FB, but poor differentiation of ML-2 cells. These data suggest that different mechanisms are involved in the differentiation of ML-2 and PLB-985 cells.
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PMID:Effects of bone marrow fibroblasts on the proliferation and differentiation of myeloid leukemic cell lines. 749 67

Adhesion is known to prime neutrophils for physiological activation in response to cytokines and other stimuli. We have employed the technique of receptor cross-linking to study the potential role of CD18, the common beta-subunit of the beta 2-integrin family of adhesion molecules, in the regulation of the respiratory burst, as measured by luminol-enhanced chemiluminescence and iodination, in human neutrophils. CD18 cross-linking primed neutrophils to activate the respiratory burst after stimulation with tumor necrosis factor alpha (TNF-alpha) (100 units/mL), formylmethionyl-leucyl-phenylalanine (fMLP) (1 microM), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 micrograms/mL), but not granulocyte colony-stimulating factor (G-CSF) (1 micrograms/mL), interferon-gamma (IFN-gamma) (100 U/mL), or phorbol myristate acetate (100 nM). The maximal rate of chemiluminescence induced by fMLP, TNF-alpha, and GM-CSF was enhanced 8-, 6-, and 1.5-fold, respectively, following CD18 cross-linking. Priming of the respiratory burst by direct engagement of CD18 was confirmed in neutrophil-mediated iodination experiments, where iodination induced by TNF-alpha, fMLP, and GM-CSF was increased 15-, 20-, and 7-fold, respectively, by CD18 cross-linking. Immunoblot experiments demonstrated that TNF-alpha-induced tyrosine phosphorylation was both accelerated and more intense in neutrophils after cross-linking of CD18. Major tyrosine phosphoprotein products include proteins with approximate molecular masses of 40, 70, and 110 kDa. Genistein (50 microM), a selective tyrosine kinase inhibitor, reduced the TNF-alpha-stimulated respiratory burst by > 80% whether or not CD18 was cross-linked. These results affirm the importance of CD18 in adhesion-dependent priming of neutrophil functions and demonstrate that CD18 engagement per se is sufficient to prime neutrophils for cytokine-induced signal transduction mediated by tyrosine phosphorylation.
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PMID:Cross-linking of CD18 primes human neutrophils for activation of the respiratory burst in response to specific stimuli: implications for adhesion-dependent physiological responses in neutrophils. 749 67

CD34 is a marker for pluripotent stem cells also present on lineage-committed hematopoietic progenitors from bone marrow and a subpopulation of immature thymocytes. To characterize these early immature thymocytes, we have studied 24 pediatric thymus samples for CD34/7 expression. Three subpopulations could be defined from these T-cell receptor (TcR-) immature thymocytes: CD34+7++ (12.0 +/- 5.8), CD34-7++ (12.6 +/- 8.6), and CD34-7+ (71.5 +/- 17.0%). CD7++ represents upregulation of this antigen and is expressed by cells of a blast-like morphology. Three-color flow cytometric analysis of these three subsets suggests the following ordered differentiation sequence: CD34+7++1-4-8-45RA+-->CD34+7++1+ 4+8-45RA+/- -->CD34-7++1+4+8-+45RO+-->CD34-7+1++4+8+45RO+. Early immature thymocyte cell division is essential in the thymus to generate a large number of precursors before the initiation of the selection process. We observed that both CD2 as well CD28 activation pathways were inefficient to serve as costimulant with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate or interleukin-2 (IL-2) to induce the proliferation of the three CD34/7 subsets isolated by cell sorting. However, whereas IL-1, IL-2, IL-3, IL-4, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were ineffective, IL-7 was a potent cytokine, alone or in synergy with stem cell factor (SCF) to induce immature thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF is restricted to the CD34+ cells and, after 4 or 8 days of culture with IL-7, some CD34+7++ acquire the expression of CD4 and/or CD8, but remain CD3/TcR-. We also tested the myeloid differentiation capacity of these CD34 immature thymocytes. Using two different approaches, myeloid colony formation in methylcellulose and limiting dilution analysis in the presence of myeloid growth factors, we were unable to detect myeloid differentiation capacity from CD34+ early thymocytes, whereas CD34+7+ from bone marrow contained about 10% of the clonogenic cells present in the CD34+7- fraction. Together, these data support the concept that thymic CD34+7++ represents the earliest thymic subset of fully committed T-lineage cells, capable of proliferating specifically to IL-7.
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PMID:CD34-expressing human thymocyte precursors proliferate in response to interleukin-7 but have lost myeloid differentiation potential. 750 22

We have previously demonstrated that protein production and mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-3 are decreased in activated mononuclear cells (MNC) from human umbilical cord compared with adult peripheral blood. Reduced production of these colony-stimulating factors (CSF) during states of increased demand, as occurs during overwhelming bacterial infection, may play a role in the pathogenesis of neutropenia and thrombocytopenia in the newborn. To determine whether the reduced mRNA expression and CSF production from activated cord MNC is secondary to the decreased transcriptional activity of the corresponding genes, we determined the transcriptional rate of GM-CSF, G-CSF, IL-3, and M-CSF by nuclear run-on assays. Cord and adult MNC were isolated by Ficoll-Hypaque density centrifugation. A total of 10(8) MNC from cord and adult blood were stimulated as follows: GM-CSF and G-CSF [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 2 mg/L phytohemagglutinin for 6 h]; IL-3 [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 0.5 mumol/L A 23187 for 6 h]; and macrophage CSF (2 micrograms/L recombinant human GM-CSF for 24 h). The nuclei from unstimulated and stimulated cells were isolated and labeled with 32P-uridine triphosphate. Newly elongated 32P-labeled RNA transcripts were hybridized to slot blots of CSF DNA. To minimize cross hybridization artifacts, short fragments (0.5-1.0 kb) of cDNA were used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcriptional rates of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, and macrophage colony-stimulating factor genes in activated cord versus adult mononuclear cells: alteration in cytokine expression may be secondary to posttranscriptional instability. 750 24


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