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 myeloid-monocytic cells ML-1, HL-60, THP-1, and U-937 were chronically infected (for > 2 years) with the lymphotropic human immunodeficiency virus type 1 (HIV-1) strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells showed a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers revealed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR, and HLA-DQ in non- or chronically infected cells. In chronically infected cells, the steady-state levels for tumor necrosis factor-alpha, interleukin (IL)-1 beta, and granulocyte-macrophage colony-stimulating factor mRNA remained unchanged whereas the one for IL-6 dropped.
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PMID:Characterization of human immunodeficiency virus-1-infected cells of myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937). 145 15

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.
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PMID:Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. 219 61

The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL-5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL.
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PMID:Response patterns of hairy cell leukemia to B-cell mitogens and growth factors. 224 29

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytokine profile was evaluated in a case of severe congenital neutropenia. The plasma levels of cytokines were measured before and during rhG-CSF therapy. These included G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha, interleukin-1 beta, interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Soluble interleukin-2 receptor (sIL-2R) was measured serially during rhG-CSF therapy. Lymphocyte subpopulations including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were also measured, rhG-CSF was administered once daily as a 30-min infusion. The patient was treated with increasing dose levels of 100, 200, 400, 800, and 1,600 micrograms/m2/day. The level of endogenous G-CSF was elevated to 334 pg/ml before treatment and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. Clinically, he showed a moderate response to a high dose of rhG-CSF (1,600 micrograms/m2/day). Plasma levels of G-CSF markedly increased during therapy but plasma levels of other cytokines did not show significant changes during therapy and lymphocyte subpopulations did not significantly change. A drastic increase in sIL-2R expression was observed after rhG-CSF infusion and an increase in sIL-2R expression occurred even before a major increase in granulocyte counts. These results showed that a high dose rhG-CSF therapy may influence the cytokine network as judged by the increased sIL-2R expression.
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PMID:Cytokine profile during high-dose rhG-CSF therapy in severe congenital neutropenia. 750 1

To obtain a better understanding of the immune response to Epstein-Barr virus (EBV), we measured the cytokines tumour necrosis factor (TNF)-alpha/beta, interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the conditioned medium of peripheral blood mononuclear cells from 10 healthy adults before and at 48 h and at 1, 2, 3 and 4 weeks following infection in vitro with EBV. Cultures were examined for regression of outgrowths of nascent virus-transformed B cells, and populations of cells in the cultures were analysed by flow cytometry. TNF-alpha/beta was not detected in infected or non-infected cultures. In infected cultures assayed at the nominated times, the highest levels of IL-2 were detected at 48 hours, IFN-gamma at 1 week, IL-6 at 2 weeks and GM-CSF between 2 and 4 weeks. IL-6 and GM-CSF, but not IL-2 or IFN-gamma, were detected in non-infected cultures but at lower levels than in infected cultures. Nine of the 10 healthy adults showed regression of outgrowths of virus-transformed B cells and, of these, seven had antibodies to the EBV capsid antigen (VCA). Strong regression was associated with sequential increases in IL-2, IFN-gamma, and low levels of IL-6 and GM-CSF. Absent or weak regression was associated with an undetectable level of IL-2, a low level of IFN-gamma, high levels of IL-6 and GM-CSF and an increased frequency of cells bearing the phenotype CD20 and HLA-DR in the final weeks of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine production in response to Epstein-Barr virus infection of peripheral blood mononuclear cells in vitro. 822 95

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

Chronic lymphocytic leukemia (CLL) cells express the CD20 antigen, and monoclonal antibodies against CD20 have resulted in remissions. We hypothezised that the anti-CD20 antibody rituximab (Rituxan) may be useful in reducing the number of contaminating CLL cells in stem cell collections for use in autologous transplantation. A pilot study in 5 patients was designed using rituximab 375 mg/m(2) as an in vivo purging step following cyclophosphamide 4 gm/m(2) and granulocyte colony-stimulating factor/granulocyte-macrophage colony-stimulating factor (G-CSF/GM-CSF) mobilization therapy for patients with advanced-stage CLL undergoing autologous stem cell transplantation. Eligible patients had 0-30% marrow involvement prior to mobilization. A single pre-rituximab leukapheresis product was obtained after the white blood cells (WBC) reached 800/mm(3) to serve as a control but was not reinfused. Rituximab was administered the following day and subsequent leukaphereses were commenced 48 h later to reach a total of >2 x 10(6) CD34(+) cells/kg. Dual-color flow cytometry CD5/CD19 and consensus PCR using primers to the joining region and FR3 of the variable region of the immunoglobulin heavy chain (IgH) were used to evaluate the degree of contaminating CLL cells in the leukapheresis product and to monitor disease status post transplant. All 5 patients were informative for the consensus PCR assay. Four of 5 patients mobilized >2 x 10(6) CD34(+) cells/kg and proceeded to cyclophosphamide 120 mg/kg and total body irradiation (6 x 200 cGy) with stem cell rescue. All leukaphereses products were positive by PCR for the IgH rearrangement and 4/5 contained CD5/CD19 dual-positive cells. Comparing the pre- and post-rituximab leukapheresis products, a reduction in the percentage of CD5(+)/CD19(+) cells was seen in 4/5 patients. All patients engrafted at a median of 13.5 days to ANC > 500/mm(3) and 11 days to platelets >20,000/mm(3). No regimen-related mortality was seen. Although 2 patients tested positive on PCR for the IgH rearrangement early after transplant, all patients had absence of the IgH gene rearrangement at 1 year and no CD5/CD19 dual-positive cells were could be detected in the bone marrow. This includes 1 heavily pretreated patient who received stem cells containing up to 30% CD5(+)/CD19(+) cells. We conclude that purging with Rituximab 48 h prior to stem cell collection was able to reduce significantly (but not eliminate) the percentage of CLL cells in the leukaphereses. However, despite the infusion of CD5(+)/CD19(+) cells in the stem cell coions, patients were able to obtain durable complete molecular remissions, implying that the PCR-positive cells in the leukaphereses may not have long-term clonogenic potential. The results also support the recommendation to test if rituximab should be part of a maintenance regimen after transplant to prevent disease recurrence in high-risk patients.
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PMID:In vivo purging with rituximab prior to collection of stem cells for autologous transplantation in chronic lymphocytic leukemia. 1198 2

High-dose intensification and autologous stem-cell transplantation (ASCT) is widely used to consolidate patients with non-Hodgkin's lymphoma (NHL), who have reached a stage of minimal residual disease. However, patients with persisting marrow and/or blood involvement and those who fail peripheral blood hemopoietic progenitor mobilization are excluded from ASCT. For such patients with no available graft to infuse, we developed 15 years ago, before the anti-CD20 monoclonal antibody therapeutic era, the use of the BEAM pretransplant regimen followed only by the administration of three cytokines (erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor). We report here on the long-term follow-up of 33 patients treated with this approach. In all, 33 NHL patients underwent the BEAM (carmustine, VP-16, cytosine-arabinoside, melphalan) followed by the administration of the three cytokines from January 1994-2000. A backup marrow, albeit infiltrated by tumor cells, had been collected earlier and stored in all. A total of 30 patients (91%) recovered normal hematopoiesis. In total, 32 patients (97%) recovered neutrophils (>500/microl) at a median of 19 days and 30 patients (91%) recovered platelets (>20,000/microl) at a median of 26 days. Age, richness of backup graft and blood-hemoglobin level at intensification had an impact on the time for hematopoietic recovery (P=0.014, P=0.014, P=0.048). The median follow-up was 62 months. Five patients died from toxicity related to the procedure. Eight patients relapsed and died. A total of 20 patients (61%) are alive, 16 (49%) in complete remission. A 5-year disease-free survival was 52+/-9%, relapse incidence 35+/-16%, mortality due to the procedure 12+/-12% and overall survival 61+/-10%. The BEAM regimen is not myeloablative. The BEAM+3CK procedure is a feasible therapeutic option that has shown efficacy in poor risk NHL patients who were not eligible for autografting because of persisting marrow/blood tumor contamination, or poor hemopoietic progenitor harvesting. It is unclear today whether some of these patients would have cleared their marrow/peripheral blood with the additional use of anti-CD20 treatment, thereby making the classical approach (BEAM followed by the infusion of a clean autograft) feasible.
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PMID:A long-term follow-up of 33 patients with non-Hodgkin's lymphoma who received the BEAM high-dose intensification regimen with cytokine support only and no transplant. 1529 7

From 1999 to 2002, 20 patients with aggressive non-Hodgkin lymphoma, among 28 who failed autologous peripheral blood progenitor cell transplantation, were rescued with cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP)/rituximab (RTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). RTX was administered twice during each course of chemotherapy, before CHOP and after GM-CSF. This cytokine was given to increase the antibody-dependent cell-mediated cytotoxicity and to reduce the leukopenia on the basis of our preliminary data, which suggested that this cytokine can upregulate CD20 expression. The relevant (World Health Organization grade 3-4) toxicity mainly consisted of myelosuppression (neutropenia in 60% of patients). Fifteen patients achieved complete remission (CR) or had a partial response, with an overall response rate of 75% (60% CR and 15% partial response). Six of the 12 patients who achieved CR relapsed: 2 died of progressive disease, 1 died of infectious complications after allogeneic transplantation, and 3 are alive in second CR. Eight patients showed progressive disease: 5 died of progressive disease, 1 of secondary acute leukemia, and 1 of infectious complications after allogeneic transplantation, whereas 1 is alive in second CR. At last follow-up, 10 patients are alive, 6 of whom are in complete continuous remission, with a median follow-up of 31 months (range, 3-51 months). The projected 4-year progression-free survival is 31.4%, and the 4-year overall survival is 50%. This new association (RTX, CHOP, and GM-CSF) was feasible in approximately 70% of patients; the overall toxicity was manageable. The good response rate and the promising outcome observed in this subset of patients could be explained by the possible increased synergy between chemotherapy, RTX, and GM-CSF, which should be explored in further studies.
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PMID:A new schedule of CHOP/rituximab plus granulocyte-macrophage colony-stimulating factor is an effective rescue for patients with aggressive lymphoma failing autologous stem cell transplantation. 1604 13

Advanced complicated atherosclerotic lesions have been related to many factors, including inflammation, infectious agents, and growth factors. Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP), inflammation, and growth factors have been associated with severe atherosclerotic lesions in necropsy material in recent work at our lab. The present study intends to clarify the pathogenesis of atherosclerosis, analyzing which of these elements (macrophages, MP, CP, lymphocytes, and growth factors) are associated with initial development of atherosclerotic lesions, discriminating elements related to stabilization of the plaque versus those related to subendothelial active accumulation of macrophages in living patients. Surgical ascending aorta fragments presenting mild atherosclerotic lesions from 30 coronary atherosclerotic patients were immunohistochemically quantified regarding CP, MP, T cells (CD4, CD8), B cells (CD20), macrophages (CD68), and growth factors [platelet-derived growth factor A (PDGF-A), PDGF-B, transforming growth factor-beta (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Cases were grouped according to the presence or not of active accumulation of macrophages at the subendothelium that indicates atheroma in development: group I (GI) fragments with <4 CD68+ cells/x400 field, in normal distribution (mean 1.8 +/- 1) representing stable atherosclerotic mild lesion, and GII fragments presenting >or=4 CD68+ cells/x400 field, in a non-normal distribution, mean (8.9 +/- 4.8, atheromas in progress), which was followed by increased number of lymphocytes. The median number in GI was significantly lower than that in GII: CD4 T (2.5 vs. 7.7), CD8 T (1.0 vs. 5.5), and CD20 B (1.5 vs. 5.5) cells/x400 field, p < 0.001. Percentage area positive for CP antigens was significantly lower in GI than in GII: 1.0 vs. 9.2, p < 0.001. There was a higher percentage area occupied by MP than CP in both GI and GII (7.8 vs. 13.8). There was no difference regarding mean number of growth factor-positive cells/x400 field: PDGF-A, 1.4 vs. 3.9; PDGF-B, 3.4 vs. 5.7; TGF-beta, 0.9 vs. 2.2; and GM-CSF, 2.0 vs. 2.2. Considering all cases, a positive correlation was seen between inflammatory cells and CP+ cells (r > 0.5 and p < 0.01). Growth factors did not correlate with inflammatory cells, CP, or MP and were usually seen in smooth muscle cell and fibrotic areas. Study of initial atherosclerotic lesions showed that MP is present in both kinds of lesion: stable and active subendothelial accumulation of macrophages. Stabilization was related to proportional increase of both infectious agents, which were also related to increased amount of PDGF-A and PDGF-B. Active macrophage accumulation lesions were related to higher elevation in CP concentration at subendothelial regions, in association with B cells, but not of MP and growth factors. MP and CP, inflammation, and growth factors, which were already described in severe atherosclerotic lesions in necropsy material, are also present in mild lesions in living patients, strongly favoring a pathogenetic role for these bacteria in the pathogenesis of atherosclerosis. Predominance of CP in relation to MP may favor progression of the plaque, which is associated with increased B-cell proliferation. PDGF-A and PDGF-B are associated with plaque stability, at least in arterial segments not prone for development of complicated lesions.
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PMID:Infectious agents, inflammation, and growth factors: how do they interact in the progression or stabilization of mild human atherosclerotic lesions? 1698 90


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