Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

The V gamma 5/V delta 1(+)-T-cell receptor (TCR)-bearing T-cell clone, 2CBET-3, was generated from C57BL/6 mice. Upon stimulation, 2CBET-3 cells produce interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, but not IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, macrophage colony-stimulating factor, or interferon-gamma. These cells were evaluated for their ability to be stimulated by a variety of murine cell lines, including fibroblasts, trophoblasts, melanoma cells, embryonic carcinomas, B-cell lymphomas, mastocytoma cells, and keratinocytes. The human B-lymphoma cell line, Daudi, also was included in these studies. We found that 2CBET-3 cells produced cytokines up to several hundredfold above the control levels in response to the B-cell lines, Daudi, and A20/2J, but not to the B-cell line 439.4.2. After fixation with glutaraldehyde, Daudi and A20/2J continued to stimulate this gamma delta T-cell line. 2CBET-3 cells also responded to the keratinocyte line PAM212, but not to another, XB-2. When lipopolysaccharides (LPS) from Escherichia coli or S. typhimurium were added to 2CBET-3 cells in the presence of A20/2J cells, 2CBET-3 cells responded with increased cytokine production compared with the cytokine production in the presence of A20/2J cells alone. 2CBET-3 cells by themselves did not respond to LPS alone or to supernatants from A20/2J cells incubated with LPS. Unlike 2CBET-3, the epidermal T-cell hybridoma 70BET-49, expressing a V gamma 5/V delta 1-TCR identical to that of 2CBET-3, did not respond to A20/2J cells in the presence or absence of LPS, suggesting a requirement for molecules other than the TCR for V gamma 5/V delta 1-TCR+ T-cell stimulation by the B-cell lines and by LPS. This unique reactivity of gamma delta-TCR+ cells is different from that of alpha beta-TCR+ cells and may reflect a functional specialization of gamma delta-TCR+ cells in the response to bacterial infections.
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PMID:Murine epidermal V gamma 5/V delta 1-T-cell receptor+ T cells respond to B-cell lines and lipopolysaccharides. 761 98

In order to elucidate the mechanisms of eosinophil differentiation, we examined the effects of combinations of interleukin 5 (IL-5) with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on in vitro differentiation into eosinophils from bone marrow cells of ICR mice. When the amount of added IL-5 was kept constant, IL-3 exhibited dose-dependent production of eosinophils both in the absence and presence of low doses of GM-CSF. In contrast, IL-5 plus GM-CSF showed highly enhanced production of eosinophils, and eosinophil production maximized at a concentration between 10 and 20 U/ml and decreased at higher concentrations. When IL-3 and GM-CSF were kept constant at concentrations of 20 U/ml and 10 U/ml, respectively, the number of eosinophils increased linearly in IL-5-dependent manner in a range from 0.3 to 30 U/ml. These results suggest that IL-3 and GM-CSF act synergistically with IL-5 in in vitro eosinophil differentiation. In addition, we propose a new method for quantifying eosinophil differentiation activity of IL-5.
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PMID:Synergism of IL-3, IL-5, and GM-CSF on eosinophil differentiation and its application for an assay of murine IL-5 as an eosinophil differentiation factor. 762 86

Leukemic cells from a patient with chronic myelocytic leukemia (CML) basophilic crisis were examined in an in vitro clonogenic assay using recombinant human hematopoietic growth factors to elucidate the proliferative and differentiative behaviors. More than 90% of the leukemic cells showed the morphologic characteristics of basophils and were positive for CD11b and CD13. The phenotype of the leukemic cells was different from that of mast cells. In the clonogenic assay using various recombinant growth factors, the leukemic cells were responsive to interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not to granulocyte-CSF (G-CSF), erythropoietin (Epo), or IL-4. IL-5 showed synergistic effects on colony formations induced by both IL-3 and GM-CSF. Transcripts of the GM-CSF receptor alpha chain gene were detected in the leukemic cells, but transcripts of the IL-4 receptor gene were not. Furthermore, c-kit and IL-7 receptor genes were expressed in the leukemic cells. Our results suggest that the differentiation pathway of basophils is different from that of mast cells, even though the receptor gene for stem cell factor (c-kit) was expressed on the basophilic leukemic cells, as it was on mast cells.
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PMID:Cellular characteristics of chronic myelocytic leukemia basophilic crisis cells: phenotype, responsiveness to and receptor gene expression for various kinds of growth factors and cytokines. 767 84

The effects of interleukin (IL)-2, -3, -4, -5, -6, and -7 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on histamine release from human basophils were evaluated. IL-3 was the only cytokine with histamine-releasing activity. This activity was observed predominantly on basophils from allergic patients (mean release +/- SEM, 33.9 +/- 9.5%; n = 12), whereas basophils from normal subjects responded less frequently to stimulation with IL-3 (mean release +/- SEM, 2.8 +/- 1.0%; n = 22). The effect of IL-3 was time and temperature dependent, since release was optimal after incubation for 120 min at 37 degrees C. When cell-bound IgE were eluted at acid pH, basophils became unresponsive to IL-3; however, IL-3-induced histamine release correlated with anti-IgE-induced histamine release in allergics, but not in normals. IL-3, IL-5, IL-6, and GM-CSF enhanced significantly anti-IgE- and FMLP-induced histamine release. In contrast, IL-2, IL-4, and IL-7 were devoid of any significant histamine-releasing or -potentiating activity. These results indicate that IL-3 can induce and IL-3, -5, and -6 and GM-CSF can enhance histamine release from human basophils, suggesting a possible role of these cytokines in the expression of allergic reactions.
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PMID:Inducing and enhancing effects of IL-3, -5, and -6 and GM-CSF on histamine release from human basophils. 768 60

The present study was designed to reexamine the interaction of granulocyte-macrophage colony-stimulating factor (GM-CSF) with endothelial cells (EC) and to investigate the expression of CSF receptor chains in these cells. In agreement with previous data, GM-CSF induced directional migration and, to a lesser degree, proliferation of human umbilical vein EC. When compared to basic fibroblast growth factor, GM-CSF was comparable in terms of chemotactic activity and was substantially less active in terms of proliferation. Binding studies confirmed the presence of receptors for GM-CSF (GM-CSFR) on EC. The expression of the beta chain common to the GM-CSFR, IL-3 receptor, and IL-5 receptor, as well as of the individual alpha chains, was studied by Northern analysis and/or reverse transcription and polymerase chain reaction. EC expressed high levels of the common beta chain transcripts. Expression of the alpha(GM) and alpha(IL-5) chain mRNA was minimal or absent in normal EC, though the transformed ECV304 endothelial cell line had substantial amounts of alpha(GM) chain mRNA. Unexpectedly, EC expressed alpha(IL-3) chain transcripts. IL-3 induced migration of EC across polycarbonate filters, whereas IL-5 was inactive.
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PMID:Differential expression of the common beta and specific alpha chains of the receptors for GM-CSF, IL-3, and IL-5 in endothelial cells. 768 96

Using a cell sorter, CD16-CD56bright natural killer (NK) cells were sorted from decidual mononuclear cells at an early stage of pregnancy. These cells were examined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method for their expression of mRNA coding for the following 12 cytokines: IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and leukemia inhibitory factor (LIF). Although mRNA coding for every cytokine was detected in decidual mononuclear cells, mRNAs coding for only G-CSF, GM-CSF, M-CSF, TNF-alpha, IFN-gamma, and LIF were detected in CD16-CD56bright NK cells. Also, the supernatant of CD16-CD56bright NK cell cultures was found to contain G-CSF, GM-CSF, M-CSF, TNF-alpha, IFN-gamma, and LIF. These findings indicate that CD16-CD56bright NK cells produce many different cytokines and that these cytokines may play an important role in a successful pregnancy.
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PMID:Cytokine production by CD16-CD56bright natural killer cells in the human early pregnancy decidua. 768 93

Interleukin-3 (IL-3) regulates growth and differentiation of multipotential as well as lineage-committed progenitor cells. The human IL-3 receptor (IL-3R) consists of the alpha and common beta (beta c) subunits. The alpha subunit (IL-3R alpha) is specific for IL-3 and binds IL-3 with low affinity. In contrast, the beta c subunit does not bind any cytokine by itself, but forms a high-affinity receptor with IL-3R alpha. As the same beta c subunit also forms high-affinity receptors for IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) with the respective cytokine-specific alpha subunit, the expression of the alpha subunits is responsible for specificity of cytokines. To examine the expression of IL-3R alpha, we have developed a monoclonal antibody (MoAb), N3A. N3A specifically bound to cells expressing IL-3R alpha and immunoprecipitated a 75 Kd glycoprotein, which became 43 Kd on N-glycosidase digestion. N3A and an anti-beta c antibody, CRS1, were used in double color fluorescence-activated cell sorter (FACS) staining with several lineage markers to see the IL-3R expression pattern in peripheral blood (PB), cord blood (CB), and bone marrow (BM) cells. Both IL-3R subunits were expressed on myeloid cell lineages (CD13+, CD14+, CD15Lo, or CD33+). To further study the IL-3R expression on hematopoietic progenitor cells, the CD34+ populations were isolated from both BM and CB cells. Those populations showed positive staining profiles with the N3A MoAb and were weakly stained with the CRS1 MoAb. Furthermore, anti c-kit antibody staining of the CD34+ fraction from CB, but not from BM, showed two intensities and the IL-3R alpha expression seemed to be higher in a fraction of low c-kit expression. Because IL-1, IL-6, G-CSF, stem cell factor (SCF), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha are known to enhance IL-3-dependent colony formation, we have examined whether this enhancement could be correlated with upregulation of the IL-3R expression. Incubation of CD34+ cells with TNF-alpha for 2 days significantly increased the level of beta c and G-CSF increased the number of cells with high level expression of alpha, while other factors did not affect the IL-3R expression. Thus, different cytokines appear to have different mechanisms for enhancement of IL-3-dependent proliferation.
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PMID:Expression and factor-dependent modulation of the interleukin-3 receptor subunits on human hematopoietic cells. 768 90

Interleukin-2 (IL-2)-dependent large granular lymphocytes (LGL) with a distinctive surface phenotype were generated from histologically normal duodenal biopsy tissues. Immunoperoxidase staining of the mucosa with an anti-CD56 monoclonal antibody revealed LGL localized in the lamina propria rather than in the epithelium. Light and electron microscopy demonstrated azurophilic and electron-dense cytoplasmic granules. Flow cytometry analysis revealed that these cells express CD45, CD56, CD2, CD7, CD11a, CD18, CD69 and the intermediate affinity (p70) IL-2 receptor (IL-2R) but not CD57, CD16, CD3, CD4, CD5, CD8, CD45RA, CD25, or the high affinity p55 IL-2R. The LGL proliferated when cultured in the presence of human rIL-2 but not in the presence of human rIL-4. Functional studies demonstrated that the LGL had strong cytotoxicity against natural killer (NK) target cells, K562, but not NK-resistant targets such as Colo 205, Melanoma and Epstein-Barr virus (EBV)-transformed B-cell lines. The LGL expressed genes for IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha) and the corresponding cytokines were detected in culture supernatant. These results provide evidence for an important role of gut mucosal LGL in the induction and regulation of inflammation and immunity in the gut.
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PMID:Morphological, phenotypic and functional characteristics of a pure population of CD56+ CD16- CD3- large granular lymphocytes generated from human duodenal mucosa. 769 28

The effects of recombinant human stem cell factor (SCF, a c-kit ligand) on an eosinophil lineage were examined in clonal and suspension cultures of human non-adherent light density bone marrow cells. Although interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-5 (IL-5) each exhibited eosinophil-colony stimulating activity, SCF did not do so alone. However, the addition of SCF to IL-3, GM-CSF, or IL-5 cultures led to an increase in the number of eosinophil colonies per 5 x 10(4) cells, from 8.0 +/- 1.4, 11.0 +/- 2.0, and 6.7 +/- 0.6, to 12.7 +/- 3.2, 19.0 +/- 4.4, and 12.0 +/- 2.0, respectively. A similar synergistic effect of SCF on eosinophils was also observed in the suspension cultures of bone marrow cells, although SCF alone had little proliferative effect. Moreover, although the delayed addition of IL-5 to cultures containing SCF led to a small increase in the number of mature eosinophils, the effect of SCF was less than that of either GM-CSF or IL-3. These observations suggest that SCF may have a proliferative effect on eosinophil precursor cells and may increase the number of mature eosinophils when used in combination with such other growth factors as IL-3, GM-CSF, and IL-5.
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PMID:Effect of c-kit ligand (stem cell factor) in combination with interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-3, on eosinophil lineage. 769 27

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells modulate allergic pulmonary eosinophilia in mice. 769 19


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