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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)

CD3- granulated leucocyte clones have been generated from human first-trimester decidualized endometrial tissue following culture in interleukin-2 (IL-2). Supernatants from both CD3- decidual granulated leucocyte (dGL) and CD3- peripheral blood natural killer (PBNK) cell clones inhibited the proliferation of choriocarcinoma cell lines. A panel of CD3- dGL clones, with or without phytohaemagglutinin stimulation, was assayed for cytokine secretion compared with CD3- PBNK clones and fresh tissue extracts. Levels of interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and IL-10 produced by stimulated CD3-CD8- dGL clones were greater than those produced by stimulated CD3-CD8+ dGL clones. In contrast, CD8+ dGL clones were more effective in production of IL-6 than CD8- dGL clones. Immunoreactive transforming growth factor-beta 2 (TGF-beta 2) was undetectable in supernatants from CD3- dGL and PBNK clones. CD3- dGL clones generally produced higher levels of all cytokines than PBNK clones. Some unstimulated CD3- dGL and PBNK clones spontaneously produced these cytokines, but usually at a reduced level. Fresh extracts of first-trimester decidual tissue contained detectable GM-CSF, TNF-alpha, IL-10,IL-6 and TGF-beta 2. Cytokine production by fresh CD3- dGL and CD3- dGL clones indicates that these cells could play an important role in the regulation of placental growth.
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PMID:Soluble mediators and cytokines produced by human CD3- leucocyte clones from decidualized endometrium. 866 42

Mast cells (MC), blood basophils (Ba) and monocytes (Mo) are of haemopoietic origin. Lineage-relationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0.716, 0.779 and 0.757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0.509; MC versus Mo, 0.625; Mo versus Ba, 0.698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R- and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0.2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI = 0.286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)alpha(CD116), CD40, Apo-1/FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)R alpha(CD123), IL-1RII(CD121b), IL-2R alpha(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.
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PMID:Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes. 867 6

We have examined the effects of irradiation on the cytokine secretion from genetically modified human esophageal and gastric carcinomas. Both cell lines were transduced retrovirally to secrete interleukin-2, interleukin-6 and granulocyte-macrophage colony-stimulating factor, respectively. The metabolism of all the transduced cells was partially inhibited by 6 Gy, and greatly inhibited by 20 Gy irradiation. Cytokine productions, however, was not affected by 6 Gy in many cases, and continued to be detected even after 60 Gy irradiation. The analysis of the dose and time of irradiation in each cytokine producer is useful for the designing of tumor vaccine using cytokine gene transfer.
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PMID:Study of irradiation effects on cytokine secretion from retrovirally-transduced tumor cells: a model for tumor vaccination. 868 10

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.
J Interferon Cytokine Res 1996 May
PMID:Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys. 872 82

We used reverse transcription-polymerase chain reaction (RT-PCR) to clone a rat complementary DNA that encoded the PVG rat granulocyte-macrophage colony-stimulating factor (GM-CSF). PCR products were cloned into a eukaryotic expression vector and transfected into the mouse myeloma cell line Sp2/0-Ag14. Cell culture supernatants of two of these transfectants supported proliferation of the growth factor-dependent cell line, DA-3, and promoted myeloid colony formation in rat and mouse bone marrow cell (BMC) cultures. The GM-CSF activity in these supernatants was neutralized by a polyclonal antibody to mouse GM-CSF. The cloning and expression of rat GM-CSF provides a valuable reagent for the study of the biology and clinical applications of the GM-CSFs.
J Interferon Cytokine Res 1995 Dec
PMID:Polymerase chain reaction cloning and expression of the rat granulocyte-macrophage colony-stimulating factor. 874 92

The presence of a novel 38 kDa protein that is tyrosine phosphorylated in human neutrophils, a terminally differentiated cell, upon stimulation of these cells with low concentrations of lipopolysaccharide (LPS) in combination with serum has been demonstrated. This 38 kDa protein was identified as the mammalian homologue of HOG1 in yeast, the p38 mitogen-activated protein (MAP) kinase. This conclusion is based on the experimental findings that anti-phosphotyrosine (anti-PY) antibody immunoprecipitates a 38 kDa protein that is recognized by anti-p38 MAP kinase antibody, and conversely, anti-p38 MAP kinase antibody immunoprecipitates a 38 kDa protein that can be recognized by anti-PY antibody. Moreover, this tyrosine phosphorylated protein is found associated entirely with the cytosol. It was also found that this p38 MAP kinase is activated following stimulation of these cells with low concentrations of LPS in combination with serum. This conclusion is based on three experimental findings. First, soluble fractions isolated from LPS-stimulated cells phosphorylate heat shock protein 27 (hsp27) in an in vitro assay, and this effect is not inhibited by protein kinase C and protein kinase A inhibitor peptides. This effect is similar to the effect produced by the commercially available phosphorylated and activated MAPKAP kinase-2 (MAP kinase activated protein kinase-2). Secondly, a 27 kDa protein that aligns with a protein recognized by anti-hsp27 antibody is phosphorylated upon LPS stimulation of intact human neutrophils prelabelled with radioactive phosphate. Lastly, immune complex protein kinase assays, using [gamma-32P]ATP and activating transcription factor 2 (ATF2) as substrates, showed increased p38 MAP kinase activity from LPS-stimulated human neutrophils. The phosphorylation and activation of this p38 MAP kinase can be affected by both G-protein-coupled receptors such as platelet-activating factor (PAF) and non-G-protein-coupled receptors such as the cytokine-coupled receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha). The effect of low concentrations of PAF is greatly increased in cells pretreated with LPS. The tyrosine phosphorylation of the p38 MAP kinase is not restricted to stimuli that mediate their actions through membrane-associated receptors, but it can be affected by agents that bypass membrane-associated receptors such as the protein translation blocker anisomycin. While anisomycin is known to increase the tyrosine phosphorylation of the 54 kDa SAPK (stress-activated protein kinase), this is the first report that shows that anisomycin also tyrosine phosphorylates the p38 MAP kinase. Cytokine receptors that increase the tyrosine phosphorylation and activation of the erk1 and erk2 MAP kinases have less effect on this p38 MAP kinase than those that do not affect the erk1 and erk2 MAP kinases. The possible role of the p38 MAP kinase in the phosphorylation of cytosolic phospholipase A2 is discussed.
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PMID:Tyrosine phosphorylation and activation of a new mitogen-activated protein (MAP)-kinase cascade in human neutrophils stimulated with various agonists. 876 79

Dendritic cells (DC) can be obtained from peripheral blood mononuclear cells (PBMC) by in vitro culture with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-13 shares properties with IL-4 but its receptor does not involve the common gamma chain present in the receptor complex of IL-4 and other cytokines. The present study was aimed to elucidate whether IL-13 can substitute for IL-4 in DC cultures and to compare the phenotypic and functional characteristics of cells obtained using these two cytokines. Monocyte-enriched PBMC were cultured with GM-CSF and IL-4 or GM-CSF and IL-13. Cell yields and DClike morphology were similar. The cells showed a membrane phenotype typical of DC (MHC II+; CD1a+; CD14-; CD3-; CD20-). IL-13-derived and IL-4-derived DC were similar in terms of macropinocytosis, stimulatory capacity of cord blood lymphocytes in mixed leukocyte reaction (MLR), and responsiveness to chemotactic signals. It is concluded that IL-13 is as effective as IL-4, combined with GM-CSF in sustaining DC differentiation from PBMC and that activation of the common gamma chain-driven transduction pathways is dispensable for DC differentiation and function.
Eur Cytokine Netw
PMID:IL-13 supports differentiation of dendritic cells from circulating precursors in concert with GM-CSF. 878 90

Monocytes/macrophages are efficient producers of alpha interferons (IFN), and IFN-gamma is a potent activator of these cells. The present study sought to investigate whether IFN-alpha affects the capacity of human monocytes/macrophages to produce IFN-alpha on induction with Sendai virus. Plastic-adherent human peripheral blood monocytes were grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 weeks during which they were transformed into macrophages. At various times, the cultures were pretreated for 24 h with IFN-gamma and induced with Sendai virus for IFN-alpha production. Pretreatment with IFN-gamma had no effect on the production of IFN-alpha during the first days in culture. The production of IFN-alpha was thereafter significantly enhanced by the IFN-gamma pretreatment. Minute amounts of IFN-gamma, < or = 0.1 IU/ml, increased the production of IFN-alpha in macrophages cultured for more than 7 days. The cooperation between IFN-gamma and IFN-alpha in macrophages may play a role in the antiviral defense of the body.
J Interferon Cytokine Res 1996 Jun
PMID:IFN-gamma enhances production of IFN-alpha in human macrophages but not in monocytes. 880

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that takes part in the growth and differentiation of normal and leukemic hematopoietic cells. Because of its potential significance in the etiopathogenesis of myeloid leukemia, we have studied the extracellular stimuli leading to GM-CSF secretion from a human myeloid leukemia cell line, K-562, and have demonstrated an important role for the cytokine in the differentiation process of this cell line. TNF-alpha, IL-1 beta, phorbol ester (PMA), and calcium ionophore A23187 were found to stimulate GM-CSF production from K-562 cells. PMA caused the cells to differentiate into megakaryocytic lineage, whereas treatment with A23187 resulted in increased expression of monocyte/macrophage marker CD14. Neutralization of the GM-CSF activity in the culture medium, as well as blocking of its receptors, resulted in suppression of the increase in CD14 expression and partially restored the proliferative capacity in cells exposed to A23187. Autocrine GM-CSF secretion did not appear to play an important role in PMA-induced megakaryocytic differentiation. These results suggest that autocrine GM-CSF secretion may be associated with differentiation of myeloid leukemic cells without any significant growth stimulatory activity.
J Interferon Cytokine Res 1996 Jun
PMID:Stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production and its role as an autocrine inducer of CD14 upregulation in human myeloid leukemia cells. 880 3

Murabutide is a synthetic muramyl peptide which is in clinical stage of development. Its effect on cytokine production was analysed in human whole blood to reproduce the natural environment. Induced gene transcription within 2 h was associated with the release of cytokines such as tumour necrosis factor (TNF), interleukin-1 beta (IL-1 beta), IL-6, IL-8, and also the anti-inflammatory mediator IL-1ra. This synthesis was not associated with the release of IL-4, IL-12, interferon gamma (IFN-gamma), the three colony-stimulating factors (CSFs) or the soluble TNF receptors. The same series of cytokines were assayed to determine the effect of some recombinant cytokines in association with murabutide. Thus, in the presence of IL-2, IL-6, IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF), the level of cytokines induced by murabutide was enhanced with no change in the other cytokines profile. IL-3 and GM-CSF were more potent in increasing the murabutide-induced response, eliciting synergistic effects on IL-8 and IL-1Ra production, at both the mRNA accumulation and the protein release. Although neither IL-12 nor IFN-gamma were produced in cells stimulated with murabutide alone, some mRNA expression was found with combined treatments. The results indicate that association of murabutide with a cytokine could exert synergistic effects, thus reducing effective doses of the recombinant protein, increasing the release of anti-inflammatory mediators, and triggering efficient cellular immunity.
Cytokine 1996 Aug
PMID:Selective potentiation of cytokine expression in human whole blood by murabutide, a muramyl dipeptide analogue. 889 42


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