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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)

Myeloblasts derived from the peripheral blood of a patient with acute myelogenous leukemia (ORL47) were found to represent the malignant counterpart of the newly elucidated monocyte-dendritic cell colony-forming unit (mono-DC-CFU). The specific cytokine conditions require to achieve intermediate and terminal maturation of DCs and monocytes from these progenitors were defined. With tumor necrosis factor (TNF) + granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor treatment numerous colony-like clusters developed. In contrast with normal DC development, further advancement of mono-DC-CFU and terminal DC maturation from the leukemic cells were dependent on the addition of interleukin-6. Functional and phenotypic analysis showed that the capacity to differentiate was maintained fully in the DC compartment, but only partially in the monocyte compartment, as judged by the lack of CD14 surface expression. Cells found at intermediate stages of DC development were potent stimulators of a mixed leukocyte reaction, a function usually attributed to mature DCs. As previously shown for normal DC development, antibodies to TNF alpha and GM-CSF blocked proliferative responses and DC growth. The importance of these observations in the classification of leukemias, normal DC development, and potential clinical strategies is discussed.
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PMID:Identification of a malignant counterpart of the monocyte-dendritic cell progenitor in an acute myeloid leukemia. 794 77

Placental macrophages were isolated and cultured in vitro to investigate their susceptibility to HIV infection and possible role in vertical transmission of HIV. After 10 days of in vitro culture the cells were positive for nonspecific esterase and acid phosphatase and negative for myeloperoxidase and placental alkaline phosphatase. They expressed cell surface HLA-ABC, HLA-DR, CD45, as well as CD68 intracellularly, as detected by flow cytometry, confirming their macrophage lineage. Approximately 80% of cells expressed surface CD14. CD4 antigen was expressed at very low levels and was confirmed by antibody blocking experiments. Infection of placental macrophage cultures with HIV resulted in a transient peak of viral replication 3 to 7 days after infection, but no later rise in HIV was detected with culture of up to 60 days. HIV replication was not up-regulated by coculture with phytohemagglutinin-stimulated lymphocytes or by treating infected cultures with tumor necrosis factor alpha or granulocyte-macrophage colony-stimulating factor.
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PMID:HIV infection of placental macrophages: their potential role in vertical transmission. 808 96

After 3-4 weeks culture of human bone marrow cells in medium supplemented with IL-3, macrophage- (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), the firmly adherent cells exhibited the morphologic features of mononuclear phagocytes and were strongly esterase-positive. Flow cytometric analysis revealed a rather homogeneous cell population with marked autofluorescence; the large majority of the cells expressed CD14, CD11a, b, and c, Fc receptors for IgG, Fc gamma RI, II, and III, and HLA class II molecules. Interferon-gamma (IFN-gamma), bacteria, and bacterial products modulated expression of some of the surface markers, induced and/or enhanced respiratory burst, phagocytic activity, secretion of tumour necrosis factor, and tumouricidal activity; in contrast, these cells were not able to generate reactive nitrogen intermediates.
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PMID:Mononuclear phagocytes from human bone marrow progenitor cells; morphology, surface phenotype, and functional properties of resting and activated cells. 841 80

The most effective antigen-presenting cells for T lymphocytes are dendritic cells (DCs), the differentiation pathway of which, however, is incompletely characterized. We examined here how DCs differentiated from human cord blood CD34+ progenitor cells cultured with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and stem cell factor. After 5 days, 2 of 3 nonadherent cells were CD13hiHLA-DRhiCD4+, half of them were also CD14+, and < or = 10% were CD1a+. When day-5 sorted CD13hiCD1a- and CD13lo cells were further cultured, CD1a+ cells appeared in the already CD13hi population, whereas CD13hi cells, a minority of which rapidly became CD1a+, emerged from the CD13lo population. By day 12, still 66% of bulk cells in suspension were CD13hi, most of which displayed high forward and side scatters of large granular cells. Half of CD13hi cells were CD1a+. All CD13hi cells expressed to the same extent DR, CD4, costimulatory and adhesion molecules, and various amounts of CD14. CD1a+ cells stimulated allogeneic lymphocytes more than CD13hiCD1a- cells and, although they were CD14+, both cell types were nonspecific esterase-negative nonphagocytic cells and were stronger mixed leukocyte reaction stimulators than were their macrophage counterparts. Eventually, the percentage of CD1a+ cells decreased. However, typical CD1a+ DCs still emerged in culture of sorted day-12 CD13hiCD1a- cells, and adding interleukin-4 to bulk cultures at that time led to the persistence of the CD1a+ population while diminishing CD14 expression. Thus, this system results first in the differentiation of CD13hi precursors that strongly express DR and CD4, from which more mature CD1a+ DCs continuously differentiate all along the culture period.
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PMID:Human dendritic cell differentiation pathway from CD34+ hematopoietic precursor cells. 855 75

A panel of two poorly differentiated (HA22T/VGH and SK-Hep-1) and six well-differentiated (HuH-6-cl 5, HuH-7, PLC/PRF/5, Hep G2, Hep 3B, and Tong) human hepatocellular carcinoma (HCC) cell lines were studied for the production of colony-stimulating factors (CSFs) using the granulocyte and macrophage colony formation (CFU-GM) assay, immunocytochemical staining, and Northern blotting. Medium conditioned by untreated HA22T/VGH cells contained a high level of CSFs that could stimulate the in vitro colony formation of human myeloid progenitor cells. The HA22T/VGH cell-derived CSF had an apparent molecular weight of 23 kD. Its activity could be effectively neutralized by antiserum against granulocyte-macrophage CSF (GM-CSF) but not by antibodies to other hematopoietic growth factors, including G-CSF, M-CSF, interleukin-3 (IL-3), and IL-6. Correspondingly, immunocytochemical studies using monoclonal anti-GM-CSF showed a strong positive reaction in the cytoplasm of the HA22T/VGH cells. Northern blot analysis revealed that untreated HA22T/VGH cells expressed a considerable amount of GM-CSF mRNA, confirming that GM-CSF production was constitutive. At optimal concentrations, lipopolysaccharide (LPS), IL-1beta, interferon-gamma (IFN-gamma), and tumor-promoting phorbol diester (TPA) could all stimulate HA22T/VGH cells to secrete GM-CSF. In addition to HA22T/VGH, SK-Hep-1 cells could also produce GM-CSF, although less effectively, whereas all the well-differentiated HCC cell lines tested were negative for CSF production. Morphologic, cytochemical, and immunocytochemical examinations demonstrated that both poorly differentiated CSF-producing HCC cell lines (HA22T/VGH and SK-Hep-1) were macrophage-like in morphology, possessed nonspecific esterase (NSE) activity, and expressed CD14, CD68, and HLA-DR on their surface, while all the well-differentiated HCC cell lines were epithelioid and lacked myeloid differentiation antigens. These results suggest that monocytoid features and CSF production may be differentiation markers of hepatocytes at the immature stages, amd that the HA22T/VGH and SK-Hep-1 cell lines may be valuable tools for the study of hepatic function and differentiation.
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PMID:Constitutive production of colony-stimulating factors by human hepatoma cell lines: possible correlation with cell differentiation. 859 73

CD34+ precursors in normal human bone marrow (BM) generate large numbers of dendritic cells alongside macrophages and granulocytic precursors when cultured for 12 to 14 days in c-kit ligand, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). This study reports an intermediate cell type that develops by day 6, and has the potential to differentiate into either macrophages or dendritic cells. When the d6 progeny are depleted of mature macrophages and residual CD34+ precursors, a discrete CD14+ HLA-DR+ population persists in addition to immunostimulatory CD14- HLA-DR() dendritic cells. Half of the CD14+ HLA-DR+ population is in cell cycle (Ki-67+), but colony-forming units (CFUs) are no longer detectable. The calls are c-fms+, but lack myeloperoxidase and nonspecific esterase. They also possess substantial phagocytic and allostimulatory activity. These post-CFU, CD14+ HLA-DR+ intermediates develop into typical macrophages when recultured in the absence of exogenous cytokines. M-CSF supports up to approximately 2.5-fold expansion of macrophage progeny. In contrast, the combination of GM-CSF and TNF-alpha supports quantitative differentiation into dendritic cells, lacking c-fms, CD14, and other macrophage properties, and expressing HLA-DR, CD1a, CD83, CD80, CD86, and potent allostimulatory activity. Therefore, normal CD34+ BM precursors can generate a post-CFU bipotential intermediate in the presence of c-kit ligand, GM-CSF, and TNF-alpha. This intermediate cell type will develop along the dendritic cell pathway when macrophages are removed and GM-CSF and TNF-alpha are provided. Alternatively, it can differentiate along a macrophage pathway when recultured with or without M-CSF.
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PMID:Dendritic cells and macrophages can mature independently from a human bone marrow-derived, post-colony-forming unit intermediate. 863 19

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.
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PMID:IL-13 supports differentiation of dendritic cells from circulating precursors in concert with GM-CSF. 878 90

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.
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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

Ehrlichia chaffeensis is a recently isolated minute gram-negative obligatory intracellular bacterium of monocytes/macrophages and is the etiologic agent of human monocytic ehrlichiosis. It is not known how macrophages respond when they encounter ehrlichiae in terms of cytokine production. In this study, we examined cytokine mRNA expression by incubating E. chaffeensis with THP-1 cells and performing competitive reverse transcription-PCR (RT-PCR). At 2 h postinfection, the levels of interleukin-1beta (IL-1beta), IL-8, and IL-10 mRNAs were significant but lower than those following Escherichia coli lipopolysaccharide (LPS) stimulation. Unlike the situation with E. coli LPS stimulation, however, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha) mRNAs were not induced. Time course and dose-response studies confirmed the absence of IL-6, GM-CSF, and TNF-alpha mRNA induction with E. chaffeensis. Viable E. chaffeensis organisms were not required for IL-1beta IO, IL-8, and IL-10 mRNA induction, since heat-killed E. chaffeensis induced identical time course responses. IL-1beta, IL-8, and IL-10 mRNAs were detected for up to 21, 21, and 24 h postexposure with E. chaffeensis, respectively, which were shut off more rapidly than with LPS stimulation. Although heat treatment of E. chaffeensis had no effect, periodate treatment completely abolished the ability of E. chaffeensis to induce IL-1beta, IL-8, and IL-10 mRNAs. The capture enzyme-linked immunosorbent assay result corresponded with the RT-PCR results, showing that viable and heat-killed E. chaffeensis produced and secreted the same levels of IL-1beta and IL-8. IL-10 production was significantly reduced by heat treatment. Periodate-treated ehrlichiae did not induce production of any of the cytokines tested. Anti-CD14 monoclonal antibody and polymyxin B did not inhibit IL-1beta mRNA expression upon exposure to E. chaffeensis. The absence of TNF-alpha, IL-6, and GM-CSF mRNA induction may delay the development of a protective immune response, thereby allowing E. chaffeensis to set up residence in macrophages.
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PMID:Absence of tumor necrosis factor alpha, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis. 892 90

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


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