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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 identified two forms of the receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) made by the human choriocarcinoma cell line JEG-3 using an affinity-labeling technique. The protein was identified in the detergent-extract was 78 kDa, very similar to that of the membrane-bound GM-CSF receptor alpha chain expressed in a wide variety of hematopoietic and nonhematopoietic cells, including JEG-3. In contrast, a 62-kDa GM-CSF binding protein, or the soluble GM-CSF receptor, was identified in the supernatant of JEG-3 cells. Utilizing the same affinity labeling technique, we did not detect the soluble GM-CSF binding protein in the supernatant of several hematopoietic cell lines, such as U-937 and KG-1, which express membrane bound alpha chain as well as beta chain. The 62-kDa soluble GM-CSF receptor is produced in abundant amounts by JEG-3, but in very small amounts, if any, by hematopoietic cell lines.
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PMID:Identification of a soluble GM-CSF binding protein in the supernatant of a human choriocarcinoma cell line. 153 19

We have previously reported on stimulation of clonal growth of cell lines from human solid tumors by recombinant human interleukin 3, recombinant human granulocyte-macrophage colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor (W. E. Berdel et al., Blood, 73: 80-83, 1989; Exp. Hematol., 16: 510, 1988). Within an extensive screening program of hematopoietic growth factor activity on malignant cells, the effects of recombinant human interleukin 6 (rhIL-6) were tested on the growth (tritiated thymidine uptake and human tumor cloning assay) of 26 different human cell lines derived from a wide range of solid tumors (head and neck, 4; lung, 1; pancreatic, 1; gastric, 1; colorectal, 3; renal, 3; bladder, 1; prostate, 1; breast, 2; ovary, 2; choriocarcinoma, 1; sarcoma, 2; glioblastoma, 2; neuroblastoma, 2). rhIL-6 (dose range up to 10(4) IU/ml) caused no reproducible enhancement or inhibition of tritiated thymidine uptake by tumor cell lines from nonhematopoietic origin. Furthermore, 19 of the tumor cell lines were clonogenic in a capillary modification of the human tumor cloning assay. No reproducible stimulation of clonal growth by rhIL-6 was observed in any of the cells tested. Particularly, there was no sensitivity of those cell lines for rhIL-6, which were previously shown to be sensitive for recombinant human interleukin 3 and recombinant human granulocyte-macrophage colony-stimulating factor in this assay. On the other hand, there were no significant growth-inhibitory effects of rhIL-6 on the cell lines tested in this study. Further experiments showed no influence of neutralizing monoclonal anti-hIL-6 antibody on the growth of 3 kidney carcinoma cell lines, making autocrine growth-modulating loops for IL-6 in these lines unlikely. In conclusion, no major interactions between hIL-6 and the growth of the human malignant cell lines from nonhematopoietic origin tested were detected in this study.
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PMID:Studies on the interaction between interleukin 6 and human malignant nonhematopoietic cell lines. 185 4

Two proteins forming the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF)1 were identified and characterized. One with apparent Mr of about 80,000 was defined as alpha-chain and has Kd of 0.7-2.8 nM. The other binding molecule with apparent Mr of about 135,000 was defined as beta-chain and is related to the high-affinity binding with Kd of 10-40 pM. The binding kinetic studies confirmed that the 125I-GM-CSF associated slower to and dissociated more rapidly from the alpha-chain than the beta-chain. The alpha-chain is expressed not only on hemopoietic cells but also on full-term placental tissues, choriocarcinoma cells, and other solid tumor cells. In contrast, the distribution of the beta-chain is restricted on hemopoietic cells. The alpha-chain probably corresponds to the low-affinity GM-CSF receptor whose cDNA has been cloned and sequenced.
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PMID:Identification and cellular distribution of distinct proteins forming human GM-CSF receptor. 215 10

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) both stimulates hematopoietic precursor cells to grow as well as enhances the function of mature effector cells, such as neutrophils, eosinophils and macrophages. All of the biological actions of GM-CSF appear to be mediated via binding to a single class of high-affinity receptors present on all responsive cells. Affinity cross-linking experiments demonstrate that the same 98 kDa cross-linked species seen on other GM-CSF-responsive cells is also detected on a choriocarcinoma cell line, JAR. However, JAR cells express significantly increased numbers (10,000 sites/cell) of low-affinity (Kd approximately 1.5 nM) GM receptors. The GM-CSF receptor is a glycoprotein which binds to wheat germ agglutinin-sepharose. It is dramatically downregulated on neutrophils by phorbol esters and formyl-methionyl-leucine-phenylalanine (fMLP), but not by phosphatidylinositol-dependent phospholipase C. GM-CSF primes neutrophils for enhanced response to secondary stimuli, such as ionophore and chemotactic factors. Specifically, GM-CSF enhances 3H-arachidonic acid release, synthesis of leukotriene B4 and platelet activity factor in response to fMLP and the calcium ionophores.
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PMID:GM-CSF: receptor structure and transmembrane signaling. 215 79

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

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has been implicated in placental growth and development. In this study, we investigated the production of GM-CSF in human first trimester pregnancy by the predominant uterine lymphocyte population of decidual CD56+ NK cells (large granular lymphocytes) and the factors that influence this production using enzyme-linked immunosorbent assays (ELISAs) and bioassays, supplemented by immunocytochemistry. We have also investigated and compared production of GM-CSF by human first trimester trophoblast and by JEG-3 and JAR choriocarcinoma cells. Our data show that appreciable amounts of GM-CSF are produced in first trimester maternal decidua and that a significant component of this secretion was from decidual large granular lymphocytes (LGL). Production of GM-CSF by LGL was constitutive and considerably greater than that of freshly isolated peripheral blood leukocytes. GM-CSF secretion by decidual LGL could be enhanced by co-culture on a monolayer of decidual stromal cells, and could also be increased in a dose-dependent manner by stimulation with interleukin-1 (IL-1) or IL-2. IL-4, IL-6, tumour necrosis factor alpha (TNF alpha), transforming growth factor beta (TGF beta), interferon alpha (IFN alpha) and IFN gamma individually had no effect on GM-CSF secretion, although IL-4, TGF beta and IFN alpha all inhibited the action of IL-2. IFN gamma had no effect on the IL-2-induced GM-CSF secretion, but did antagonize the action of IL-1. Normal human first trimester trophoblast was also found to produce GM-CSF, although no production whatsoever was seen by JEG-3 or JAR choriocarcinoma cells. These results suggest that GM-CSF from uterine lymphocytes, and from trophoblast itself, may influence placental growth and development in both a paracrine and an autocrine manner.
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PMID:Production of granulocyte-macrophage colony-stimulating factor by human trophoblast cells and by decidual large granular lymphocytes. 753 Jul 25

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has also been implicated in placental growth and development. In this study we have performed a detailed immunohistological localization of the low affinity GM-CSF receptor (GM-CSF-R alpha) in human first trimester implantation site and non-pregnant endometrium. We have also investigated receptor expression and GM-CSF binding in vitro by normal first trimester trophoblast using flow cytometric analysis and compared this with JEG-3 and JAR choriocarcinoma cells. In the first trimester, the GM-CSF-R was found to be present on villous cytotrophoblast and all populations of extravillous trophoblast. Expression by villous syncytiotrophoblast was weak or absent, but this increased markedly by term. GM-CSF-R were also expressed by fetal Hofbauer cells within the mesenchyme of the chorionic villi and by uterine glandular epithelium and decidual macrophages within maternal decidua. GM-CSF-R was not expressed by glands in proliferative phase endometrium but began to appear during the secretory phase, suggesting hormonal regulation of the receptor on uterine glandular epithelium. Flow cytometric comparison of normal isolated first trimester trophoblast and JEG-3 and JAR choriocarcinoma cells revealed two- to threefold higher surface expression of GM-CSF-R by choriocarcinoma cells and higher binding capacity for rhGM-CSF than normal trophoblast. These results suggest that GM-CSF may regulate growth and development of human trophoblast. GM-CSF may also influence placental development and function by acting via decidual and fetal macrophages, and uterine glandular epithelium, which are the other cell populations to express the receptor.
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PMID:Demonstration of the low affinity alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSF-R alpha) on human trophoblast and uterine cells. 793 90

Activated monocytes and lymphocytes secrete cytokines that act as autocrine and paracrine mediators to promote and regulate local immune processes. These cell types are abundant at the maternal-fetal interface, and cytokines may play a role in pregnancy maintenance or failure. The purpose of this study was to determine the effects of selected monocyte- and lymphocyte-derived cytokines on trophoblast progesterone and estradiol production. JEG-3 choriocarcinoma cells were cultured in supplemented medium alone or in various concentrations of selected recombinant monocyte or lymphocyte cytokines. The cytokines were evaluated both individually and in combination. After 48 h of incubation, the culture supernatant was aspirated and stored at -20 C. Samples were then analyzed for steroid concentration by specific RIAs. Specific interleukin-1 (IL-1)-and tumor necrosis factor (TNF)-neutralizing antibodies were evaluated for their ability to abrogate the cytokine's observed stimulatory effect. To evaluate the physiological relevance of the progesterone-stimulating effect observed with monocyte-derived cytokines, JEG-3 cells were incubated with activated monocyte supernatant or directly cocultured with activated monocytes, and supernatants from these cultures were analyzed for progesterone levels. The monocyte cytokines [IL-1 alpha (5 U/mL), IL-1 beta (5 U/mL), and TNF alpha (1000 U/mL) significantly stimulated trophoblast progesterone production (nanograms per mL): JEG-3 control, 4.1 +/- 0.5; IL-1 alpha, 7.8 +/- 0.9; IL-1 beta, 8.8 +/- 0.5; and TNF alpha 7.2 +/- 0.8 (P < 0.05). Neither the monocyte nor the lymphocyte cytokines altered trophoblast estradiol production. Activated monocyte supernatant and direct JEG-3-monocyte cocultures also significantly stimulated trophoblast progesterone production in vitro. The stimulatory effect of the monocyte-derived cytokines was specific, as demonstrated by neutralization assay. The increased trophoblast progesterone production was not due to enhanced cellular proliferation, but to enhance cellular steroidogenesis, as measured by quantitative DNA analysis. The lymphocyte cytokines (IL-2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor had no effect on trophoblast progesterone production. We conclude that monocyte IL-1 alpha, IL-1 beta, and TNF alpha may regulate trophoblast progesterone production through paracrine effects. Monocyte-trophoblast interactions may be significant in normal pregnancy as well as pregnancy disorders.
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PMID:Cytokine regulation of trophoblast steroidogenesis. 812 30

Scatchard binding analysis has been employed to characterize expression of low-affinity receptors for tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by isolated human placental syncytiotrophoblast microvillous plasma membrane (StMPM) vesicles. Trophoblastic receptors for the c-kit ligand (stem cell factor) could not be identified using the same methods. No high-affinity receptors could be detected for GM-CSF or IFN-gamma, but a minority of high-affinity TNF-alpha receptors were identified. Cross-inhibition studies indicated the low-affinity receptors to be specific for each cytokine rather than to be non-specific cytokine-binding factors. Only relatively high-affinity receptors for TNF-alpha and IFN-gamma could be detected on the BeWo human choriocarcinoma cytotrophoblast cell line, whereas receptor affinity for GM-CSF was similar to that on syncytiotrophoblast. Immunohistochemical staining has confirmed expression of IFN-gamma receptor by syncytiotrophoblast: in contrast, staining for the established TNF-R1 and TNF-R2 receptors was associated mainly with placental vascular endothelium. These low-affinity cytokine receptors could reflect unique biological responses of foetal syncytiotrophoblast in the presence of local concentrations of maternal cytokine.
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PMID:Low-affinity receptors for tumour necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor are expressed on human placental syncytiotrophoblast. 840 76

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


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