UNIPROT:P04141 - FACTA Search

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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)

Human bone marrow-derived progenitor cells were studied in a long-term bone marrow culture system (LTBMC) dependent on an autologous stroma cell layer. The establishment of the stromal cell layer was facilitated by using marrow obtained from small pieces of sternum, which was cultured for 4 weeks without addition of exogenous growth factors. After this period, the response of LTBMC to two different cytokines [recombinant human interleukin-2 (rhIL-2) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)] was investigated. Our results show proliferation in response to both cytokines and induction of differentiation of cells able to bind IL-2 and/or GM-CSF again. The two cytokines also generate cells responding to rhGM-CSF by colony formation. However, a difference with respect to morphology, phenotype and cytotoxic function of cells in the LTBMC, was noted between the two cytokines. Cells with large granular lymphocyte (LGL) morphology and cytotoxic activity against K562 and Daudi were generated only in the rhIL-2-supplemented LTBMC. This was compatible with a higher frequency of cells expressing the CD56+ phenotype in the IL-2-stimulated LTBMC as compared to the GM-CSF supplemented LTBMC. Our results also demonstrate the existence of a population of myeloid progenitor cells (CD33+) with ability to bind IL-2 in fresh bone marrow (BM).
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PMID:Natural killer (NK) cell activity in human long-term bone marrow cultures (LTBMC): effects of interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the progenitor cells. 163 51

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to a culture of human peripheral blood mononuclear cells in the presence of interleukin 2 (IL-2) in vitro to elucidate its effect on the induction of lymphokine-activated killer (LAK) cells. Viable cell counts of cultured cells and their cytotoxic effects against natural killer (NK) cell-resistant Daudi cells and NK cell-sensitive K562 cells were measured using the trypan blue dye exclusion test and a 51Cr release assay from the tumor cells, respectively. Although GM-CSF alone did not influence either the cytotoxicities or the surface phenotypes of the cultured cells, the viable cell counts were significantly increased by the addition of GM-CSF in the presence of IL-2 (P less than 0.01). These findings indicate that the addition of GM-CSF in the presence of IL-2 during the induction of LAK cells is useful for obtaining a larger number of effector cells which possess substantial cytotoxic activity.
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PMID:The effects of recombinant human granulocyte-macrophage colony-stimulating factor on the induction of lymphokine-activated killer cells in vitro. 178 73

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by IL-2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells, as assessed by the 4 hr 51Cr-release assay. For determination of the role of GM-CSF in LAK induction, highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated from MNC by counter-flow centrifugal elutriation (CCE). Pre-treatment of monocytes for 4 days with GM-CSF before addition of lymphocytes plus IL-2 resulted in a significant dose-dependent increase in monocyte-mediated up-regulation of LAK induction, but in the absence of monocytes GM-CSF had no effect on LAK cell induction. Similarly, GM-CSF augmented the proliferative response of lymphocytes to IL-2 in the presence of monocytes as assessed by 3H-TdR uptake. Treatment with anti-GM-CSF antibody completely abolished up-regulation of LAK induction by GM-CSF-treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM-CSF-responding monocytes were found to be responsible for up-regulation of LAK induction. These results suggest that GM-CSF may be important in monocyte-mediated up-regulation of LAK cell induction in vivo.
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PMID:Up-regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of induction of lymphokine (IL-2)-activated killer (LAK) cells by human blood monocytes. 266 33

The present investigation demonstrates that leukoregulin, a cytokine secreted by natural killer (NK) lymphocytes up-regulates the sensitivity of tumor cells to lymphokine-activated killer (LAK) cell cytotoxicity. It has been previously established that leukoregulin increases the sensitivity of sarcoma, carcinoma and leukemia cells to natural killer (NK) cell cytotoxicity. Tumor cells were treated with leukoregulin for 1 h at 37 degrees C and tested for sensitivity to NK and LAK cytotoxicity in a 4-h chromium-release assay. NK-resistant Daudi, QGU and C4-1 human cervical carcinoma cells became sensitive to NK cytotoxicity after leukoregulin treatment, and their sensitivity to LAK was increased two- to sixfold. Y-79 retinoblastoma cells, which are moderately sensitive to NK and very sensitive to LAK, became increasingly sensitive (two- to four-fold) to both NK and LAK cell cytotoxicity. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant interleukin-1 (alpha and beta), recombinant interferon gamma, recombinant tumor necrosis factor or combinations of the latter two failed to up-regulate tumor cell sensitivity to NK and LAK cell cytotoxicity. However, treatment with recombinant interferon gamma for 16-18 h, GM-CSF and interleukin-1 beta for 1 h induced a state of target cell resistance to both NK and LAK cell cytotoxicity. Leukoregulin may have an important physiological function in modulating NK and LAK cell cytotoxicity by increasing the sensitivity of target cells to these natural cellular immunocytotoxicity mechanisms.
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PMID:Leukoregulin up-regulation of tumor cell sensitivity to natural killer and lymphokine-activated killer cell cytotoxicity. 268 71

Interleukin 2 (IL-2), produced with and without co-stimulation by the Burkitt's lymphoma line Daudi, was purified 37,000-fold to apparent homogeneity from lymphocyte conditioned medium by (NH4)2SO4 precipitation, DEAE-cellulose ion-exchange chromatography, gel filtration, and chromatography on blue agarose and on Procion-red agarose. The purified IL-2 showed a 10(6) U/mg protein sp act. IL-2 produced in the absence of Daudi cells had a mol wt of 26,000 as measured by gel filtration and an isoelectric point of 6.7. This IL-2 showed a 16,000 and 17,000 mol wt in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). IL-2, produced in the presence of Daudi cells (10(6)/ml), showed a mol wt of approximately 14,000, as measured by both gel filtration and SDS-PAGE, and an isoelectric point of 8.1. The purified IL-2 lacked detectable interferon (alpha and gamma), granulocyte-macrophage colony-stimulating factor, B cell growth factor, T cell-replacing factor, and thymocyte-differentiating activity and was free of any contaminating proteins as judged by silver staining in SDS-PAGE. All three molecular forms of IL-2 were biologically active at concentrations of 10(-11) - 10(-10) M, supporting the growth of human and murine cytotoxic T cell lines.
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PMID:Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. 698 Feb 56

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in augmentation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) from pleural cavity mononuclear cells (PCMNCs) was examined in sixteen patients with resectable primary lung cancer not associated with malignant effusion. None of the patients had received any anticancer therapy prior to this study. Incubation of PCMNCs of patients without malignant effusion with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer-resistant Daudi cells. This result was obtained by using the 4 h 51Cr-release assay. PCMNCs and blood mononuclear cells (BMNCs) were harvested simultaneously from pleural cavity lavage fluid and peripheral blood in lung cancer patients. The LAK activity developed from PCMNCs and BMNCs following incubation with IL-2 for 4 days, but the LAK activity from PCMNCs was significantly lower than that from BMNCs (P < 0.05). Incubation of PCMNCs with GM-CSF augmented the LAK activity from PCMNCs to a level as high as that from BMNCs. These results suggest that the combined use of GM-CSF with IL-2 may result in augmentation of LAK activity developed from PCMNCs of lung cancer patients without malignant effusion.
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PMID:Granulocyte-macrophage colony-stimulating factor augments lymphokine-activated killer activity from pleural cavity mononuclear cells of lung cancer patients without malignant effusion. 759 64

It has been shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce specific and non-specific anti-tumour cytotoxicity and also stimulates the proliferation and function of peripheral lymphocytes and thymocytes. GM-CSF and interleukin 2 (IL-2) act synergistically on peripheral lymphocytes for the induction of a highly effective cytotoxic cell population. Thus, the goal of our investigation was to study the effects of GM-CSF upon expansion, proliferation and in vitro killing activity of tumour-infiltrating lymphocytes (TILs) from renal cell carcinoma (RCC). TILs from seven consecutive tumours were cultured with GM-CSF (500 or 1000 nmol ml-1) without IL-2 supplementation, with suboptimal doses of IL-2 (8 and 40 U ml-1) plus GM-CSF (1000 nmol ml-1), and with a dose of IL-2 (400 U ml-1) which sufficed alone to induce TIL development plus GM-CSF (500 or 1000 nmol ml-1). GM-CSF alone or together with suboptimal doses of IL-2 was not able to induce or facilitate TIL development in these cultures. When GM-CSF at both concentrations studied was added to optimal doses of IL-2 the resulting TIL populations proliferated significantly better and faster (+66%), resulting in a higher cell yield (+24%) at the time of maximal expansion of the TIL cultures. The length of the culture periods of TILs was not affected by GM-CSF when compared with the control cultures supplemented with IL-2 alone. In vitro killing activity of TIL populations stimulated with IL-2 and GM-CSF remained unspecific, but lysis of the autologous tumour targets as well as the allogeneic renal tumour targets was significantly enhanced (+138%) as compared with the corresponding control TILs stimulated with IL-2 alone. Lysis of the natural killer (NK)-sensitive control cell line K562 and the NK-resistant Daudi cell line remained unchanged even though FACS analysis of TILs cultured with IL-2 and 1000 nmol of GM-CSF demonstrated a significantly higher proportion of cells expressing the CD56 molecule (+50%). Specific receptors for GM-CSF could not be demonstrated on TILs from RCC. Our data demonstrate that GM-CSF alters the biological behaviour of IL-2-activated TILs from renal cell carcinoma in terms of proliferation, in vitro killing activity and cell-surface molecule expression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of granulocyte-macrophage colony-stimulating factor on tumour-infiltrating lymphocytes from renal cell carcinoma. 759 37

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 the present study, we investigated the differentiation of human NK cells from bone marrow, cord blood and mobilized peripheral blood purified CD34+ stem cells using a potent culture system. Elutriated CD34+ stem cells were grown for several weeks in medium supplemented with stem cell factor (SCF) and IL-15 in the presence or absence of a murine stromal cell line (MS-5). Our data indicate that IL-15 induced the proliferation and maturation of highly positive CD56+ NK cells in both types of culture, although murine stromal cells slightly increased the proliferation of NK cells. NK cells differentiated in the presence of MS-5 were mostly CD56+ CD7 and a small subset expressed CD16. These in vitro differentiated CD56+ NK cells displayed cytolytic activity against the HLA class I- target K562. The CD56+ CD16+ subset also lysed NK-resistant Daudi cells. Neither of these NK subsets were shown to express Fas ligand. Total CD56+ cells expressed high amounts of transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor, but no IFN-gamma. Investigation of NK receptor expression showed that most CD56+ cells expressed membrane CD94 and NKG2-A mRNA. PCR analysis revealed that p58 was also expressed in these cells. The role of CD94 in NK cell-mediated cytotoxicity was assessed on human HLA-B7-transfected murine L cells. While a low cytotoxic activity towards HLA-B7 cells was observed, the HLA-DR4 control cells were killed with high efficiency. These studies demonstrate that cytolytic and cytokine-producing NK cells may be derived from adult and fetal precursors by IL-15 and that these cells express a CD94 receptor which may influence their lytic potential.
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PMID:NK cells differentiated from bone marrow, cord blood and peripheral blood stem cells exhibit similar phenotype and functions. 964 81

Several antigens, including the products encoded by the genes MAGE-1 and MAGE-3, are recognized on human melanoma cells by HLA-A1, HLA-A2, or HLA-Cw*1601*-restricted T cells on autologous or HLA-matched melanoma cell lines. T-cell recognition of naturally processed MHC class I-presented peptides, or alternatively synthetic peptides derived from MAGE-1 or MAGE-3, leads to cytokine release as well as to a cytotoxic T-cell response in these antimelanoma-directed polyclonal or clonal effector T-cell populations. Recent reports suggest that the activity of T lymphocytes infiltrating melanoma in vivo appears to be impaired. We report here the characterization of the in vitro (in the presence of 6000 IU interleukin 2) expanded tumor-infiltrating lymphocyte (TIL) T-cell line PM2-B2 derived from a patient with rapidly progressing and therapy-resistant head and neck melanoma. The TIL cell line PM2-B2 did not lyse, but instead released granulocyte-macrophage colony-stimulating factor in response to the autologous tumor or HLA-A1-matched allogeneic tumor cell lines. The TIL line PM2-B2 did not kill the MHC class I natural killer/lymphokine-activated killer target cell lines Daudi or K562. The fine specificity of the TIL line PM2-B2 restricted by HLA-A1 was further characterized by evaluating specific granulocyte-macrophage colony-stimulating factor release in response to MHC class I-eluted peptides derived from HLA-A1(+) melanoma cell lines. TIL PM2-B2 failed to recognize the recently described HLA-A1-presented peptides derived from the gene products encoded by MAGE-1 or MAGE-3. PCR-based analysis of the freshly harvested tumor from patient PM2-B2 revealed the presence of message for the melanoma-associated gene products MAGE-1 and MAGE-3, but not for tyrosinase or MART-1/MELAN-A. Acid elution and high performance liquid chromatography fractionation of MHC class I-presented peptides from HLA-A1-matched melanoma cell lines 397 or 888 revealed that TIL PM2-B2 recognized at least three distinct peptide epitopes eluting in high performance liquid chromatographic bioactive fractions 5/6, 36, and 51/52. These bioactive peaks appeared to be shared among HLA-A1(+) melanoma cell lines. We suggest, based on this report, that HLA-A1-presented melanoma-derived peptides (other than those previously reported peptides derived from MAGE-1 or MAGE-3) may represent targets for TIL recognition as defined by cytokine release, but not cytotoxicity. Such an immune response differentially defined by cytokine release, but absent cytotoxic functions, may either reflect the impaired cytolytic function of the TIL population or reflect the inherent nature of HLA-A1-presented melanoma T-cell epitopes leading to cytokine release, but not to a cytotoxic T-cell response. Additionally, this report suggests that the individual T-cell immune response to melanoma may be rather complex, involving diverse T-cell effector functions (e.g., cytotoxicity or cytokine release), each of which should be evaluated in studies of antitumor-specific T-cell reactivity.
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PMID:Detection of naturally processed and HLA-A1-presented melanoma T-cell epitopes defined by CD8(+) T-cells' release of granulocyte-macrophage colony-stimulating factor but not by cytolysis. 981 95

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