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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)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are weak inducers of major histocompatibility complex (MHC) class II expression on purified human blood monocytes. The glucocorticoid dexamethasone synergizes with GM-CSF or IL-3 for the upregulation of HLA-DR, -DP and -DQ antigen mRNA and cell-surface expression by these cells. The purpose of the present study was to address the mechanism of dexamethasone action. We demonstrate that the capacity of dexamethasone to up-regulate GM-CSF-induced MHC class II expression correlates with the capacity to up-regulate GM-CSF receptor, but not the interferon-gamma (IFN-gamma) receptor, in a highly dose-dependent manner on monocytes. Although dexamethasone induces GM-CSF receptor expression, it does not confer responsiveness to IL-5, a cytokine that shares a common chain of its heterodimeric cytokine receptor signalling molecule with IL-3 and GM-CSF. Three other steroid hormones, beta-oestradiol, vitamin D3 and dehydroepiandosterone (DHEA), were also tested for their capacity to up-regulate MHC class II expression. All three mediators failed to enhance MHC class II expression or GM-CSF receptor expression on the surface of human monocytes. These experiments suggest that dexamethasone may act to up-regulate GM-CSF-induced MHC class II antigen expression on monocytes by up-regulating cytokine receptor expression.
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PMID:Dexamethasone up-regulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes. 783 47

Dendritic cells (DC) isolated from the lymph nodes or spleens of mice and pulsed with contact sensitizers or protein antigens stimulate primary proliferative responses by syngeneic T cells and responses to alloantigens in the mixed leucocyte reaction (MLR). Using enriched human peripheral blood DC, we attempted to stimulate primary immune responses to contact sensitizers by autologous lymphocytes in vitro. No significant proliferation above background levels or CD69 expression (an early activation antigen on lymphocytes) was detected despite using a wide range of donors, chemicals, antigens and cell concentrations. Culture of DC for up to 5 days in vitro in the presence of phytohaemagglutinin (PHA)-conditioned culture supernatants, or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) also failed to induce primary proliferative responses to contact sensitizers. Comparisons were made between blood and lymph node DC from mice to explore whether the lack of stimulation was the result of differences between mouse and human DC or between DC isolated from different tissues. DC from lymph nodes stimulated primary responses to contact sensitizers in both blood and lymph node lymphocytes whereas blood DC did not stimulate responses. Both lymph node and blood DC stimulated an allogeneic MLR, although blood DC were less efficient than those from lymph node. The data show that DC from different tissues exhibit variable functional activity. DC from blood and lymph nodes were examined to determine whether surface antigen expression is related to functional activity. Murine blood DC expressed similar levels of LFA-1, LECAM-1 and CD44 compared with lymph node DC but lower levels of MHC class II, B7 and ICAM-1. These results may therefore have important implications for antigen processing and presentation in cells from different tissue compartments.
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PMID:Differential function of dendritic cells isolated from blood and lymph nodes. 783 50

The hematopoietic growth factors interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) regulate the survival, maturation, and activation of eosinophils. Corticosteroids in contrast have a negative effect both on the hematopoietic process and the function of eosinophils. We have unexpectedly observed synergy between IL-5 and glucocorticoids such as dexamethasone and hydrocortisone for induction of the MHC class II antigens HLA-DR and HLA-DP on eosinophils isolated from human blood. Similarly glucocorticoids enhanced GM-CSF and IL-3, but not interferon gamma (IFN gamma), induced expression of these antigens. Expression of a third MHC class II molecule, HLA-DQ, was not induced on eosinophils by any of the cytokines alone, but in one of three donors tested, IL-3 plus dexamethasone induced high levels of expression. Although cytokine-induced expression of the accessory molecule intercellular adhesion molecule 1 (ICAM-1) was partially inhibited by glucocorticoids, cytokine- and dexamethasone-treated eosinophils presented antigen more efficiently to a hemagglutinin peptide-specific T-cell clone than eosinophils treated with cytokine alone. These results highlight a potential new role for endogenous or exogenous glucocorticoid hormones in enhancing MHC class II expression by eosinophils.
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PMID:Synergy between dexamethasone and interleukin-5 for the induction of major histocompatibility complex class II expression by human peripheral blood eosinophils. 791 86

Binding of superantigens to MHC class II molecules results in transduction of biochemical signals leading to cellular activation and gene expression. We demonstrate that the staphylococcal superantigens toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA) activate HIV-1-LTR-driven transcription of chloramphenicol acetyl transferase in the human monocytic cell line THP-1. Induction of HIV-1-LTR-driven transcription in THP-1 cells by superantigens was associated with the induction of nuclear factor-kappa B DNA-binding activity. Superantigens also increased viral protein secretion from the granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1. Induction of HIV-1 gene expression in monocytic cells by superantigens occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms. Our results suggest that superantigens and other MHC class II ligands may activate HIV-1 gene expression in monocytes/macrophages.
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PMID:Superantigens activate HIV-1 gene expression in monocytic cells. 806 48

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.
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PMID:Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. 846 20

The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Dendritic cells (DC), with their potent antigen-presenting and accessory activities, are involved in the stimulation of naive T cells. To examine the biological functions of DC, we developed a method for generating large numbers of murine splenic DC. First, DC were propagated in vivo by using a granulocyte-macrophage colony-stimulating factor-secreting tumor as a continuous in vivo source of the cytokine. The DC enriched in the spleen, especially in the white pulps, were purified after an overnight culture. We could reproducibly obtain 6 to 10 X 10(6) splenic DC per mouse. These DC were morphologically similar to interdigitating cells, expressed high levels of MHC class II and costimulatory molecules, and were highly allo-stimulatory in mixed lymphocyte reactions. Further analysis on T cell stimulation activity revealed that the DC had strong costimulatory activity on human T cells. Activated B cells, which express both B7-1 and B7-2, had little T cell costimulatory activity under the same assay conditions. A human histiocytic leukemia cell line, U937, that showed only weak costimulatory activity by itself, worked synergistically with DC and further intensified the T cell stimulation by DC. These findings suggest the presence of a T cell costimulation mechanism in DC, which is activated synergistically by monocytes or macrophages, and deserves further study.
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PMID:GM-CSF-induced in vivo expansion of splenic dendritic cells and their strong costimulation activity. 877 79

The authors analysed the antigen-presenting ability of eosinophils purified from peritoneal exudate cells of interleukin-5 (IL-5) transgenic mice. The granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated eosinophils induced proliferative responses of primed lymph node T cells and thymus T cells to staphylococcal enterotoxin B (SEB), while untreated eosinophils induced little or no response. GM-CSF-treated eosinophils also induced proliferation of ovalbumin (OVA)-primed lymph node T cells to OVA. Although untreated eosinophils expressed no MHC class II molecule on the surface the eosinophils could be induced to express major histocompatibility complex (MHC) class II molecules when treated with GM-CSF. In the present study, anti-I-Ak monoclonal antibodies (MoAbs) strongly inhibited proliferation of thymus T cells and proliferation of OVA-primed lymph node T cells in response to OVA, but weakly inhibited proliferation of primed T cells in response to SEB. Furthermore, CD80 (B7-1) and CD86 (B7-2) were expressed on the surfaces of untreated eosinophils. The expression of those two molecules on the eosinophils was increased by incubation with GM-CSF. Moreover, anti-CD80 or anti-CD86 MoAbs blocked proliferative responses of primed lymph node T cells and thymus T cells to SEB, and also blocked responses of primed lymph node T cells to OVA. Thus, CD80 and CD86 play an important role in stimulation of T cells by eosinophils.
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PMID:Requirement of CD80 and CD86 molecules for antigen presentation by eosinophils. 879 16

Juvenile myelomonocytic leukemia (JMML) carries a poor prognosis. The endogenous production of cytokines by the JMML cells contributes to their growth and therapeutic resistance. Interleukin (IL)-4, IL-10, and IL-13 inhibit cytokine production in monocytes. We have now studied whether these cytokines can inhibit JMML cell cytokine production, thereby potentially reducing the malignant cell load in this disorder. We found that IL-10, but not IL-4 or IL-13, dose dependently inhibited JMML cell production of the hemopoietic growth factors granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and IL-1beta. Similarly, IL-10, but not IL-4 or IL-13, suppressed JMML colony formation and cell viability. This was not due to the absence of receptors because we could detect mRNAs for the IL-4 and the IL-13 receptor alpha subunits and the IL-2 common gamma subunit in JMML cells. Furthermore, the receptors were active since both IL-4 and IL-13 up-regulated surface expression of MHC class II and down-regulated CD14 antigens on JMML cells and monocytes. Unlike activated monocytes, the JMML cells did not produce IL-10. It is suggested that the loss of cytokine inhibitory effects of IL-4 and IL-13 could play a role in the pathogenesis of this disorder. On the other hand, the inhibition of cytokine production, growth, and viability of JMML cells by IL-10 suggests that this cytokine may have a therapeutic potential in JMML.
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PMID:Interleukin (IL)-10, but not IL-4 or IL-13, inhibits cytokine production and growth in juvenile myelomonocytic leukemia cells. 901 77

The extreme host specificity of pathogenic neisseriae limits investigations aimed at the analysis of bacterial-host interactions almost completely to the use of in vitro models. Although permanent epithelial and endothelial cell lines are already indispensable tools with respect to initial infection processes, studies concerning the interaction of neisseriae with phagocytic cells have been confined to primary human blood cells. We investigated the use of human leukemia-derived monocytic and myelomonocytic cell lines that can be differentiated in vitro towards phagocytic cells by a panel of chemical and biological reagents including cytokines, vitamin analogs, and antileukemia drugs. Whereas tumor necrosis factor alpha, gamma interferon, bufalin, or granulocyte-macrophage colony-stimulating factor only marginally increased the ability of monocytic MonoMac-6 and myelomonocytic JOSK-M cells to interact with the bacteria, retinoic acid and vitamin D3 treatment for 2 to 4 days led to highly phagocytic cells that internalized gonococci in an Opa protein-specific manner. This is comparable to the phagocytosis by primary monocytes from human blood, where more than 80% of cells are infected with intracellular bacteria. The increased phagocytic activity of JOSK-M cells following in vitro differentiation was paralleled by enhanced oxidative burst capacity. Whereas undifferentiated cells responded to neither phorbol 12-myristate 13-acetate nor other known soluble and particulate stimuli, cells incubated with retinoic acid and bufalin showed the same pattern and the same intensity of oxidative burst activity in response to Neisseria gonorrhoeae as primary cells: Opa-expressing gonococci elicited an oxidative burst, whereas Opa- gonococci did not. The surface expression of major histocompatibility complex (MHC) class II molecules was only slightly changed after retinoic acid treatment. Also, phagocytosis of gonococci had no influence on MHC class II surface expression. Taken together, our results demonstrate that in vitro-differentiated human myelomonocytic JOSK-M cells provide a suitable model for the study of a variety of aspects of the gonococcal interaction with phagocytes.
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PMID:An in vitro-differentiated human cell line as a model system to study the interaction of Neisseria gonorrhoeae with phagocytic cells. 912 73


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