Gene/Protein Disease Symptom Drug Enzyme Compound
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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 studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells. These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.
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PMID:Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors. 137 88

We compared the effect of haematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, IL-3, and IL-5 on the functional activation of human eosinophils and neutrophils from the same donor. All four colony-stimulating factors (CSF) enhanced the phagocytosis of Candida albicans by eosinophils and increased staphylococcal, but not Candida, killing. GM-CSF and IL-5 had a profound stimulating effect on eosinophil staphylocidal activity. GM-CSF and IL-3 enhanced the generation of leukotriene C4 (LTC4) induced by calcium ionophore A23187 and the release of arylsulphatase and beta-glucuronidase from specific and small granules of eosinophils. In contrast, IL-1 and IL-5 had no effect on degranulation. GM-CSF and IL-1 enhanced phagocytosis of C. albicans by neutrophils, and GM-CSF stimulated degranulation and the release of the enzymes beta-glucuronidase and arylsulphatase from neutrophils while IL-1 stimulated the release of arylsulphatase only. This study indicates that the eosinophil-active colony-stimulating factors can markedly enhance the host defence function of the eosinophil and even make it the equal of the neutrophil in staphylocidal activity. The CSF-activated eosinophil, however, may cause inappropriate inflammation and normal tissue damage.
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PMID:Activation of human eosinophil and neutrophil functions by haematopoietic growth factors: comparisons of IL-1, IL-3, IL-5 and GM-CSF. 155 Jul 68

Previously, we have shown that Escherichia coli alpha-hemolysin represents a potent stimulus for inflammatory mediator release (O2- release, beta-glucuronidase release, and leukotriene generation) from human polymorphonuclear granulocytes (PMN) as well as for histamine release from a human lymphocyte-monocyte-basophil cell suspension (LMB). In contrast, the E. coli alpha-hemolysin leads to a downregulation of cytokine release (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-1 beta) from human LMB. This study was undertaken (i) to analyze the priming efficacy of growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF] and granulocyte CSF [G-CSF]) on inflammatory mediator release from human PMN and LMB challenged with hemolysin-producing E. coli bacteria as well as with cell-free E. coli alpha-hemolysin and (ii) to identify major components involved in GM-CSF and G-CSF priming. GM-CSF pretreatment led to an increased chemiluminescence response from human PMN by up to 100%, leukotriene B4 generation was enhanced up to fivefold, and histamine release from human LMB increased from 45% +/- 15% to 75% +/- 5% (mean +/- standard distribution) of the total histamine content. G-CSF priming induced an increase in the chemiluminescence response by up to 50% +/- 5% from human PMN and an increase in histamine release from human LMB by 20% +/- 5%. The growth factors, GM-CSF and G-CSF, modulated neither beta-glucuronidase release from human PMN nor IL-8 release from human PMN and LMB challenged with the E. coli alpha-hemolysin. GM-CSF and G-CSF pretreatment increased the fluoride (NaF)-induced chemiluminescence response by up to 10-fold; the serine/threonine phosphatase inhibitor okadaic acid inhibited GM-CSF- and G-CSF-induced priming. NaF-induced histamine release was enhanced up to 60 and 30% by GM-CSF and G-CSF priming, respectively. GM-CSF and G-CSF pretreatment did not modulate phorbol 12-myristate 13-acetate-induced chemiluminescence response or histamine release. GM-CSF by itself induced an increase in 5-lipoxygenase-specific mRNA expression within 5 min. Our results indicate that (i) GM-CSF and G-CSF interact with inflammatory cells via distinct cellular signalling, (ii) the signal transduction pathway is dependent on the cellular mediator, and (iii) the use of growth factors may be a potent tool to influence the clinical outcome in infectious diseases.
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PMID:Effect of growth factors on Escherichia coli alpha-hemolysin-induced mediator release from human inflammatory cells: involvement of the signal transduction pathway. 751 12

Human neutrophils were activated by the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) to produce superoxide (O2-) and to release the primary granule enzyme beta-glucuronidase and the predominantly secondary granule enzyme lysozyme. Pretreatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) increased the secretion of all three substances upon addition of fMLP. The augmentation by GM-CSF was significantly attenuated by the 5-lipoxygenase inhibitor AA861 and by the guanylate cyclase inhibitor LY83583. The secretion induced by fMLP alone was much less affected by either of the two inhibitors. AA861 inhibited leukotriene B4 production in neutrophils primed with GM-CSF and stimulated with fMLP, and LY83583 inhibited GM-CSF-evoked increases of 3',5'-guanosine monophosphate. The data suggest that activation of lipoxygenase and guanylate cyclase is not critical to the fMLP stimulation pathway, but they may be important components of the pathway by which GM-CSF augments neutrophil responses to fMLP. However, AA861 and LY83583 may have important actions in addition to inhibition of 5-lipoxygenase and guanylate cyclase.
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PMID:Effects of inhibition of lipoxygenase and guanylate cyclase on human neutrophil responses to formyl peptide and granulocyte-macrophage colony-stimulating factor. 810 55

Downregulation of MHC class I molecules is believed to be often the cause of tumor immune escape and at the same time it is the major obstacle to T-cell based immunotherapy of tumors. In our experimental model, the C57BL/6 mice bearing tumors induced by TC-1/A9 cells characterized by expression of HPV16 oncogenes and downregulation of H-2b molecules were immunized with highly immunogenic E7GGG.GUS DNA vaccine expressing the fused gene of modified HPV16 E7 (E7GGG) with E.coli beta-glucuronidase (GUS). The DNA vaccine was administered by gene gun on days 7 and 14 after s.c. injection of tumor cells. The tumors in situ were injected with recombinant vaccinia virus MVA expressing the gene for murine granulocyte-macrophage colony-stimulating factor (MVA-GM-CSF). Two doses of the DNA vaccine combined with at least two consecutive local treatments with MVA-GM-CSF were able to inhibit significantly the growth of tumors. We have shown by ELISPOT-IFNgamma that in situ expression of the GM-CSF gene did not enhance the E7 specific systemic Tcell response. We found that local injections of MVA-GM-CSF induced an increase of intratumoral CD3+ T cell counts and that the DNA vaccination resulted in up-regulation of MHC type I molecules on tumor cells in vivo. We suppose that i.t. delivery of MVA-GM-CSF changed the local tumor microenvironment and rendered tumors more attractive and better accessible to effector T cells.
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PMID:Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules. 1782 23