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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)

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.
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PMID:Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series. 284 93

Supernatants of cultured human thymic nonlymphoid cells were assayed for granulopoietic factors using cultures of low density bone marrow mononuclear cells (LD-BMMC). Thymic nonlymphoid cell-conditioned medium (TNLC-CM) supported vigorous myeloid colony growth of LD-BMMC, and of LD-BMMC depleted of T lymphocytes and/or monocytes. Colony stimulating activity (CSA) in TNLC-CM was abrogated by a highly specific neutralizing antiserum against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). TNLC-CM also enhanced colony growth in LD-BMMC stimulated by colony stimulating activity from a giant cell tumor culture (GCT). The enhancing activity of TNLC-CM, unlike its CSA activity, required the presence of adherent cells in the marrow cell culture. The addition of anti-interleukin-1 (anti-IL-1) antibody to TNLC-CM inhibited the GCT-enhancing activity, but not the CSA. When the anti-IL-1 immunoglobulin was added directly to cultures of thymic nonlymphoid cells, GM-CSF production was completely inhibited, and the GCT enhancing activity was neutralized. We conclude that an intercellular regulatory network exists in cultured thymic explants in which GM-CSF expression is induced by IL-1. In this system, the granulopoietic effect of IL-1 derives not from a direct effect on myeloid progenitors, but from its ability to recruit CSA production by other cells.
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PMID:Granulocyte macrophage colony-stimulating activity production by cultured human thymic nonlymphoid cells is regulated by endogenous interleukin-1. 304 37

In this study microglial cells isolated from brain cell cultures of newborn mice were characterized and investigated for morphology, their responses to growth factors and their functional properties. The microglial cells were phagocytic, contained nonspecific esterase activity and expressed Fc (IgG1/2b) and type-3 complement receptors. Scanning electron microscopy revealed that in analogy to brain tissue two types of microglial cells are present in the cultures: the ameboid and the ramified type which both display similar appearance by transmission electron microscopy. Interleukin 3 and the granulocyte-macrophage colony-stimulating factor were potent growth factors for the cultured microglial cells. The cells were negative for class II antigens (Ia) of the major histocompatibility antigen complex. However, upon treatment with interferon-gamma (IFN-gamma) microglial cells became Ia+ and functioned as antigen-presenting cells when tested on ovalbumin-specific Ia-restricted helper T cells. Furthermore, microglial cells exposed to IFN-gamma and endotoxin developed tumor cell cytotoxicity and produced tumor necrosis factor alpha. Taken together, microglial cells share the characteristics of cells of the macrophage lineage.
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PMID:Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. 311 91

We detected constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in 3 human solid tumors by Northern blot analysis. Two of them were also found to secrete the GM-CSF protein by colony forming unit-culture assay. Southern blot analysis of each tumor DNA showed no gross rearrangement of the GM-CSF gene. This is the first report that demonstrates expression of the GM-CSF gene in solid tumors at the mRNA level.
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PMID:Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in human solid tumors. 311 35

Bone marrow-derived cells from C3H/HeJ mice were cultured in the presence of recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) or highly purified murine macrophage colony-stimulating factor (CSF-1) for 7 days. Following this 7-day culture period, mature macrophages were harvested and replated at precise densities in the absence of exogenous rGM-CSF or CSF-1, and assayed in a two-signal tumoricidal assay. Cultures were stimulated with medium only or with combinations of recombinant interferon-gamma (rIFN-gamma) as the "priming" signal, and/or butanol-extracted lipopolysaccharide (But-LPS) as the "triggering" signal for 24 hr. At this time, 51Cr-labeled, P815 tumor target cells were added, and the percent tumor cell cytotoxicity was determined after 16 hr. Macrophages derived under the influence of rGM-CSF exhibited significant tumoricidal capacity with medium alone (16 +/- 5%). The addition of "priming" signal only (i.e., rIFN-gamma, 10.0 U/ml) significantly increased tumoricidal capacity to 31 +/- 9%. Treatment with But-LPS alone did not alter the basal tumoricidal activity of rGM-CSF-derived macrophages. Combinations of rIFN-gamma (10.0 U/ml) and But-LPS (0.5-5.0 micrograms/ml) generated highly tumoricidal macrophages (50-60% tumor cell cytotoxicity). In contrast, medium-treated CSF-1-derived macrophages exhibited a significantly lower basal level of tumor cytotoxicity (6 +/- 3%). Unlike rGM-CSF-derived macrophages, treatment of CSF-1-derived macrophages with high concentrations of rIFN-gamma alone did not increase significantly the level of cytotoxicity above that of medium-treated cultures. However, CSF-1-derived macrophages responded to the highest concentrations of But-LPS (5.0 micrograms/ml) to increase tumoricidal activity from 6 +/- 3% to 17 +/- 5%. Optimal tumoricidal activity (44 +/- 17%) was observed when CSF-1-derived macrophages were treated simultaneously with high concentrations of both rIFN-gamma and But-LPS. Thus, macrophages derived from bone marrow progenitors in either rGM-CSF or CSF-1 exhibited tumoricidal capacities that differed in basal activity as well as in their requirements for and sensitivities to "priming" and "triggering" signals.
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PMID:Bone marrow progenitors cultured in the presence of granulocyte-macrophage colony-stimulating factor versus macrophage colony-stimulating factor differentiate into macrophages with distinct tumoricidal capacities. 313 73

Three macrophage cell lines from bone marrow cells of C3H/HeN mice were isolated by successive transfer of the cells in culture with L-cell-conditioned medium (LCM) or WEHI-3 cell-conditioned medium (WEHI-3CM). These cell lines, which express Fc receptors, are involved in Fc-mediated phagocytosis and possess nonspecific esterase activity. Two (BDM-1 and BDM-2) of three cell lines show dependency for growth on either macrophage colony-stimulating factor (M-CSF) (CSF-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and do not respond to interleukin 3 (IL-3). The third clone (BDM-3) proliferates in response to IL-3 as well as to GM-CSF and weakly responds to M-CSF and to interleukin 4 (IL-4). GM-CSF, in combination with the suboptimal concentration of M-CSF, acted synergistically on the proliferation of BDM-1 cells. The tumor-promoting phorbol diester, 12-o-tetradecanoyl-phorbol-13-acetate (TPA) also acted synergistically with the three CSFs (IL-3, GM-CSF, and M-CSF) to stimulate the proliferation of BDM-1 cells. The synergistic effect was observed when cells were pretreated with TPA and subsequently stimulated with IL-3. The calcium ionophore A23187 enhanced the proliferation of BDM-1 cells costimulated with TPA and IL-3. These factor-dependent macrophage cell lines should be useful for studying signal transduction mechanisms in the regulation of cell growth.
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PMID:Establishment and characterization of factor-dependent macrophage cell lines. 314 56

Reticulum cell sarcomas (RCS) of SJL mice are completely dependent on host cells for their growth and therefore fail to grow in vitro. RCS cells induce marked proliferation in SJL Ly-1+2- T cells accompanied by lymphokine production. In an attempt to fully understand the host-tumor cell interaction, an RCS cell line, cRCS-X, was established in vitro from a transplantable tumor by the addition, every 3 wk, of gamma-irradiated syngeneic lymph node (LN) cells to the culture. cRCS-X maintains all of the characteristics of the parent tumor, RCS-X, including cell surface phenotype (Ks and I-As positive, Ds negative and B cell marker 14.8 positive), ability to stimulate host T cells, and ability to grow in nonirradiated but not in gamma-irradiated SJL mice. The growth factor requirements of cRCS-X were examined. It was found that human BCGF can replace gamma-irradiated LN cells in the maintenance of long term in vitro growth of cRCS-X. cRCS-X cells respond to human B cell growth factor (BCGF) or to recombinant murine interleukin (IL)-5 in a short term proliferation assay [( 3H]thymidine incorporation) in a dose-dependent manner in the presence and absence of fetal calf serum. BCGF also promotes colony formation in soft agar by cRCS-X cells. Although both IL-1 and interferon-gamma can synergize with BCGF in the induction of cRCS-X proliferation, these lymphokines, as well as IL-2, IL-3, granulocyte-macrophage colony-stimulating factor, and IL-4 have no effect on cRCS-X growth when added alone. In addition, it was shown that SJL LN cells produce both IL-4 and BCGF II activities as assayed on murine B cells, after stimulation with gamma-irradiated cRCS-X cells. In light of these results it is postulated that IL-5, [corrected] produced by syngeneic T cells [corrected] after stimulation with RCS, is essential for RCS growth, both in vitro and in vivo.
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PMID:Characterization and growth factor requirements of SJL lymphomas. I. Development of a B cell growth factor-dependent in vitro cell line, cRCS-X. 327 20

Purified biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances antibody-dependent cell-mediated cytotoxicity (ADCC) of human neutrophils toward human promyelocytic leukemia cells (HL-60), B-lymphoma cells, and human T-leukemia virus II-infected human B-lymphoblastoid cells. The stimulation of antibody-dependent cell-mediated cytotoxicity is rapid (less than an hour), occurs at picomolar concentrations of GM-CSF, and does not require the presence of GM-CSF during the killing reaction. Therefore, neutrophils may be targeted toward tumor cells by antibody and their tumoricidal activity enhanced by GM-CSF in vitro. These results suggest that GM-CSF may have therapeutic utility in cancer therapy by increasing the number and activity of effector cells directed toward tumors by receptors to the immunoglobulin Fc fragment.
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PMID:Biosynthetic granulocyte-macrophage colony-stimulating factor enhances neutrophil cytotoxicity toward human leukemia cells. 331 47

WEHI-274 is a monocytic leukemia that arose in a BALB/c mouse infected with Abelson murine leukemia virus. A series of subclones were derived from early passages of this tumor. Three subsets of these leukemogenic subclones were identified. Two subsets demonstrated autostimulatory patterns of growth. This was due to the ectopic production of the T-cell lymphokine the panspecific hemopoietin IL-3 in one case and of the T-cell lymphokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in the other. The third type of subclone did not secrete any autostimulatory growth factor. In the subclone producing IL-3, one copy of IL-3 gene was rearranged and abnormal IL-3 RNA transcripts were present in the nucleus. Subclones producing GM-CSF also contained abnormal GM-CSF RNA transcripts, although no rearrangement of the GM-CSF gene was detected. All three sets of subclones shared a common rearrangement of one c-myb oncogene, suggesting that they share a common ancestor. These results suggest that initiation or progression of leukemogenic behavior in this abnormal clone occurred in three different ways, two of which involved autostimulation by the ectopic activation of T-cell lymphokine genes.
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PMID:Autostimulatory mechanisms in myeloid leukemogenesis. 347 68

Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) was purified to homogeneity from medium conditioned by COS cells transfected with a cloned human GM-CSF cDNA and shown to be an effective proliferative stimulus in human marrow cultures for GM and eosinophil colony formation. The specific activity of purified rH GM-CSF in human marrow cultures was calculated to be at least 4 X 10(7) U/mg protein. Clone transfer experiments showed that this proliferation was due to direct stimulation of responding clonogenic cells. Acting alone, rH GM-CSF did not stimulate erythroid colony formation, but in combination with erythropoietin, increased erythroid and multipotential colony formation in cultures of peripheral blood cells. rH GM-CSF had no proliferative effects on adult or fetal murine hematopoietic cells, did not induce differentiation in murine myelomonocytic WEHI-3B cells, and was unable to stimulate the survival or proliferation of murine hematopoietic cell lines dependent on murine multi-CSF (IL 3). rH GM-CSF stimulated antibody-dependent cytolysis of tumor cells by both mature human neutrophils and eosinophils and increased eosinophil autofluorescence and phagocytosis by neutrophils. From a comparison of these effects with those of semipurified preparations of human CSF alpha and -beta, it was concluded that rH GM-CSF exhibited all the biologic activities previously noted for CSF alpha.
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PMID:Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. 348 28


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