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 effects of human interleukin 3 (IL-3), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied on the functional activity of human peripheral blood monocytes from healthy individuals and from eight patients at 4, 8 and 12 weeks following autologous bone marrow transplantation (ABMT). Functions studied included superoxide production, phagocytosis of Candida albicans and reduction of 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl tetrazolium bromide (MTT). IL-3 and GM-CSF significantly enhanced the oxidative metabolism of monocytes from healthy individuals, while the effect of M-CSF was moderate. A considerable variability between healthy individuals was found in both resting and cytokine-stimulated monocytes with regard to superoxide production. All three investigated CSFs, i.e. IL-3, M-CSF and GM-CSF did not affect phagocytosis of C. albicans by the cells or their metabolic activity (reduction of MTT). In ABMT patients no deficit in the functional activity of monocytes was found at any time after transplantation and all three CSFs investigated did not modulate the functional activity of the cells. These results suggest that monocytes do not have a major role in infectious complications post-ABMT.
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PMID:Effects of human interleukin 3, macrophage and granulocyte-macrophage colony-stimulating factor on monocyte function following autologous bone marrow transplantation. 132 33

The effects of the inhibitor for protein kinase A or C, or tyrosine kinase (H-8, staurosporine, or genistein, respectively) on the proliferation of leukemic and normal bone marrow cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-3 (IL-3) were studied using the MTT assay. These inhibitors suppressed the proliferation of leukemic and normal bone marrow cells in a dose-dependent manner. Although the suppressive effect of each inhibitor on cell proliferation was varied in each instance, the effects were almost similar whichever CSF was added. A significant difference was not recognized between leukemic and normal bone marrow cells in terms of sensitivity to these inhibitors. The data indicate that protein kinase inhibitors have an inhibitory effect on leukemic and normal hematopoietic cell proliferation and that further studies are required to determine if this effect is due to the inhibition of protein kinases acting as the second messenger of CSFs.
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PMID:Effect of protein kinase inhibitors on the proliferation of leukemic cells stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor or interleukin-3. 171 9

The effects of human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) 1-1000 U/ml on the growth of human lung cancer cell lines have been studied in vitro. A panel of 10 small cell, 1 adenocarcinoma and 1 large cell lines was used with multidrug resistant sublines of 3 of the panel. The MTT assay was used to quantify cell numbers after 6-8 days' growth in the presence of GM-CSF. Neither growth inhibition nor stimulation of any of the cell lines in the presence of GM-CSF was observed. Any effects of this agent on residual tumour cells may not therefore present a problem during its clinical use to stimulate marrow regeneration after high-dose chemotherapy for lung cancer.
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PMID:Failure of GM-CSF to influence the growth of small cell and non-small cell lung cancer cell lines in vitro. 184 14

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.
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PMID:A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor. 220 65

To evaluate the effect of colony-stimulating factors and interferon gamma on the oxidative burst capacity of neutrophils in chronic granulomatous disease (CGD) we studied the neutrophils of a patient with variant CGD both from peripheral blood and from bone marrow culture on day 7 and 14. The results revealed that preincubation of peripheral neutrophils for 24 h in medium containing recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and recombinant human interferon gamma (rhIFN-gamma) alone or in combination did not improve the maximal oxidative burst activity measured by MTT assay. The colonies of this patient formed in agar assay were either composed of predominantly nitroblue tetrazolium (NBT)-positive cells or completely unable to reduce NBT. Despite variable colony numbers in the presence of different cytokines, the rate of NBT-positive colonies was less than 17% of the total number of colonies. However, more than 72% of the colonies were NBT positive in controls. In liquid culture, bone marrow cells yielded a comparable rate of NBT-positive and -negative populations at day 7. These data indicate that rhG-CSF, rhGM-CSF, and rhIFN-gamma alone or rhG-CSF and rhGM-CSF in combination with rhIFN-gamma are not able to reconstitute the oxidative burst defect in CGD in vitro. Indeed, regarding colony-forming capacity, the bone marrow cells from the patient responded to CSFs as well as those from control donors did. This fact may warrant the administration of hematopoietic growth factors, at least in variant CGD, in order to enhance the absolute number of functionally normal neutrophils.
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PMID:Clonal growth of functionally normal and deficient neutrophils from the bone marrow of a patient with variant chronic granulomatous disease. Lack of reconstitution of oxidative burst defect by G-CSF, GM-CSF, and IFN-gamma in vitro. 767 93

The MTT assay, a colorimetric assay, is found to be suitable for chemosensitivity testing. Recently, it has been suggested that hematopoietic growth factors (HGF) may enhance the effects of cytostatic drugs in acute myeloid leukemia (AML). We therefore studied the effects of granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with cytosine arabinoside (Ara-C), daunorubicin (DNR), mitoxantrone (MXT), or etoposide (VP-16) by using the MTT assay. The results were compared with in vitro clonogenic assays. Briefly, AML cells of nine patients were incubated in the presence or absence of G-CSF, IL-3, or GM-CSF under serum-free conditions for 24 hours. Next, for the MTT assay, Ara-C (final dilution range: 0.0024-240 micrograms/ml), DNR (final dilution range: 0.05-3.2 micrograms/ml), MXT (final dilution range: 0.05-3.2 micrograms/ml), or VP-16 (final dilution range: 0.1-100 micrograms/ml) were added and incubated for 48 hours. Cell survival was determined and IC75 values (75% reduction as compared to control cultures) were calculated. For clonogenic assays, the three lowest drug concentrations were used. After 48 hours, the clonogenic response was determined in serum-free, semi-solid cultures with G-CSF, IL-3, or GM-CSF. The results obtained by the MTT assay showed no significant enhancement of cytotoxicity by HGF on cytostatic drug preincubated cells compared to cytostatic drugs alone. The results obtained by the clonogenic assays showed increased cytotoxicity of Ara-C combined with G-CSF, IL-3, or GM-CSF. The median IC75 values of Ara-C decreased from 0.056 to 0.0168 microgram/ml with G-CSF (p = 0.01), from 0.108 to 0.0168 microgram/ml with IL-3 (p = 0.004) and from 0.12 to 0.0204 microgram/ml for GM-CSF (p = 0.02). Only moderate enhanced cytotoxicity was observed when VP-16 was combined with IL-3 (p = 0.036) or GM-CSF (p = 0.036), but not with G-CSF. No enhanced cytotoxicity of DNR and MXT to clonogenic AML cells was found when these agents were combined with HGF stimulation. The results indicate that the MTT assay underestimates HGF enhanced cytotoxicity of Ara-C or VP-16 to clonogenic cells. Therefore, the assay is not useful for accurately detecting differences of clonogenic response due to the proliferative status of cells. In this paper, the potential explanations for the failure of the MTT assay are discussed.
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PMID:Enhanced chemosensitivity in acute myeloid leukemia by hematopoietic growth factors: a comparison of the MTT assay with a clonogenic assay. 769 94

We recently found that microglia, brain macrophages, express interleukin-4 (IL-4) receptor mRNA in vitro. Since IL-4 exhibits a variety of functions on the cells of monocyte-macrophage lineage, we examined the effects of IL-4 on the functions of microglia. Recombinant IL-4 induced the proliferation of microglia in a dose- and time-dependent manner as determined by MTT colorimetric assay, [3H]thymidine uptake and bromodeoxyuridine (BrdU) incorporation. IL-4 also synergistically enhanced the proliferation of microglia with such colony-stimulating factors as IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). It also increased acid phosphatase activity and superoxide anion formation by these cells. Despite these positive effects on proliferation and activation, IL-4 suppressed the IFN gamma-induced class II MHC antigen expression in these cells. Since these effects of recombinant IL-4 were inhibited by the addition of monoclonal antibody against IL-4 receptors, the effects of IL-4 on microglia appear to be a specific function via IL-4 receptors. Although microglia and astrocytes produce a variety of immunoregulatory cytokines, neither cell produced IL-4 as determined by bioassay or detection of IL-4 mRNA by RT-PCR method. Thus, the exogenous IL-4 may contribute to the accumulation of microglia in or around inflammatory lesions in the central nervous system, and may be involved in the regulatory mechanisms of microglia.
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PMID:Interleukin-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression. 807 35

Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O2-) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml-1) for 48 h suppressed O2- release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml-1) and IFN-gamma (1.2 ng ml-1) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O2- release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis.
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PMID:Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae. 878 73

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were specifically cytotoxic to human leukemia cell lines bearing high affinity receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not toxic to mammalian hematopoietic cell lines lacking human GMCSF (hGMCSF) receptors. In receptor positive cells, cytotoxicity can be specifically blocked by a large excess of hGMCSF, confirming that its cytotoxicity is mediated through the hGMCSF receptor. THough DTctGMCSF inhibited granulocyte-macrophage colony formation by committed myeloid progenitor cells (CFU-GM), it did not significantly affect erythroid burst formation by committed erythroid progenitor cells (BFU-E), or mixed granulocyte-erythroid-macrophage-megakaryocyte colony formation by pluripotent multilineage progenitor cells (CFU-GEMM). DTctGMCSF holds promise for the treatment of myeloid lineage malignancies, and is a useful reagent to study hematopoiesis.
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PMID:A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor. 916 36

Antibiotics have previously been shown to have immunomodulatory effects. We examined the effect of the broad-spectrum fluoroquinoline antibiotic trovafloxacin on cytokine synthesis by monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or gram-positive cells (heat-killed Staphylococcus aureus [Pansorbin]). Trovafloxacin levels achievable in humans suppressed in vitro synthesis of each of the cytokines analyzed, viz., interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha. This effect was not due to direct effects of the drug on cellular viability; at these concentrations, trovafloxacin did not have demonstrable cytotoxicity for the monocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Although similar patterns of suppression of cytokine synthesis were observed in samples obtained from the same volunteers on different days, there were significant day-to-day variations. These results reveal that trovafloxacin possesses significant immunomodulatory activity in vitro and suggest that suppression of acute-phase inflammatory responses may occur in vivo, elicited through trovafloxacin's effect on cytokine synthesis by human monocytes.
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PMID:Effect of trovafloxacin on production of cytokines by human monocytes. 966 Oct 9


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