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)

Friend spleen focus-forming virus (F-SFFV) is a replication-defective retrovirus that induces a multistage erythroleukemia in mice. In the first stage, expression of the SFFV envelope glycoprotein results in erythroid hyperplasia. Subsequently, the F-SFFV integrates near the Spi-1 gene and activates its expression, resulting in immortalized cells that represent a second stage in the disease process. We report here that media conditioned by erythroleukemia cell lines or leukemic spleen cells induced by the polycythemia-inducing strain of F-SFFV (F-SFFVp), but not medium conditioned by SFFVp-induced hyperplastic spleens, promote the proliferation of normal granulocyte-macrophage progenitor cells and of granulocyte-macrophage colony-stimulating factor (GM-CSF)- and/or interleukin-3 (IL-3)-dependent cell lines. The colony-stimulating activity of the conditioned media from four of five of the lines studied was neutralized by antibodies specific for IL-3 and/or GM-CSF, and IL-3 and GM-CSF-specific mRNA could be detected in the cells after amplification by the polymerase chain reaction. No rearrangements of the IL-3 or GM-CSF genes were observed by Southern blot analysis. However, as previously shown for SFFV-induced cell lines, the Spi-1 gene was expressed in all of these cells. Because the Spi-1 gene encodes a transcription factor whose cognate sequences are present in the promoter region of many hematopoietic growth factor genes, including IL-3 and GM-CSF, Spi-1 activation may be inducing the expression of these genes.
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PMID:Expression of the interleukin-3 and granulocyte-macrophage colony-stimulating factor genes in Friend spleen focus-forming virus-induced erythroleukemia. 157 54

Sequential bone marrow biopsy specimens and peripheral blood findings were evaluated from patients treated with recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for recurrent non-Hodgkin's lymphoma. Parallel increases were found in white blood cell count and marrow cellularity and in absolute neutrophil count, monocyte count, and marrow myeloid:erythroid ratio. Platelet count recovery and the reappearance of megakaryocytes occurred later than granulocyte/monocyte recovery. Elevated peripheral eosinophil counts and eosinophilic hyperplasia in the marrow were noted during recombinant human granulocyte-macrophage colony-stimulating factor administration, as was the appearance of distinctive, prominently granulated and/or vacuolated neutrophils and neutrophilic precursors in the blood and bone marrow. No detrimental effects of recombinant human granulocyte-macrophage colony-stimulating factor administration in the marrow or peripheral blood were observed.
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PMID:Bone marrow and blood findings after marrow transplantation and rhGM-CSF therapy. 157 3

The effects on bone marrow (BM) cell proliferation and differentiation of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were studied in nine patients with malignancies without BM involvement and in three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was administered for 14 to 18 days by continuous intravenous (i.v.) infusion and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14 days. Changes induced by cytokine treatment were assessed by morphoimmunohistochemical analysis of BM biopsies. Comparison was made in the cytokine-treated groups and with control patients who received HD-CTX alone. BM cellularity and the myeloid/erythroid (ME) ratio were lower in rhIL-3-treated than in rhGM-CSF-treated patients, but in both groups it was significantly higher than in the controls. The proportion of BM cells stained by PC10, a monoclonal antibody (MoAb) recognizing a proliferation-associated nuclear protein (PCNA), increased from 6.78% to 21.18% (P less than .02) after rhIL-3, and from 5% to 35.33% (P less than .001) after rhGM-CSF; no increase was observed in the control group. The frequency of CD34+ BM cells was unchanged after rhIL-3 (P = NS) and decreased after rhGM-CSF (P less than .001). In both groups, most of the PC10+ cells were represented by promyelocytes and myelocytes with no increase in blast cell numbers. rhIL-3-treated BM showed an increased number of megakaryocytes and increased proliferative activity of erythroid cells as compared with rhGM-CSF cases. BM stroma changes observed in both treated groups included endothelial cell proliferation, increased BM macrophage concentration, and increase in BM fibroblasts as detected with an anti-nerve growth factor receptor antibody. In most rhIL-3-treated cases, BM fibrosis developed after treatment. The same effect was not observed in rhGM-CSF patients.
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PMID:Recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor administered in vivo after high-dose cyclophosphamide cancer chemotherapy: effect on hematopoiesis and microenvironment in human bone marrow. 158 13

We studied the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in 13 patients with acute myeloid leukemia (AML) and one patient with refractory anemia with excess of blasts in transformation using the AML blast (AML colony-forming units, AML-CFU) and mixed (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) colony culture assays. In parallel, these patients received GM-CSF s.c. at 125 micrograms/m2/day, or in escalated doses starting with 10 micrograms/m2/day for a week or until circulating blast counts reached 50 x 10(9)/liter, in an effort to sensitize leukemic blasts to cell-cycle-specific agents. Results of in vivo GM-CSF treatment were correlated with those of in vitro assays. In 9 of 12 patients (75%), GM-CSF treatment increased peripheral blood blast counts (in vivo effect). GM-CSF also stimulated in vitro AML blast colony proliferation in these nine patients and increased the S+G2M phases of the cell cycle in five out of five of these patients' samples. Two of three patients in whom an in vivo response could not be demonstrated also failed to have a detectable in vitro response. These observations suggest that the AML blast colony culture assay may be useful in predicting the response of AML to cytokine therapy. Finally, GM-CSF stimulated granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid (erythroid burst-forming units, BFU-E) colony proliferation in 14 and 11 patients, respectively, including the 3 individuals who demonstrated no clinical effect on blast counts. It is, therefore, possible that GM-CSF may be used to stimulate proliferation of progenitors that differentiate into mature granulocyte, monocyte-macrophage, and erythroid cells.
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PMID:Comparison of in vivo and in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute myeloid leukemia. 158 2

We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3-containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL-3, IL-4, IL-6, G-CSF, and GM-CSF.
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PMID:Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation. 161 Oct 96

We recently reported the production and characterization of four monoclonal antibodies (MoAbs) against rat platelet glycoprotein IIb/IIIa (GPIIb/IIIa). In this study we developed a simple and efficient three-step procedure, based on positive selection by immunoadsorption (panning) using one MoAb, P55, to purify rat megakaryocyte colony-forming cells (megakaryocyte colony-forming units, CFU-MK) from normal bone marrow. Cells obtained after each step were assayed for their ability to form megakaryocyte colonies in the presence of Concanavalin A (Con A)-stimulated rat spleen cell-conditioned medium in soft agar cultures. Marrow cells were first separated on discontinuous Percoll gradients. Cells sedimented at densities between 1.063 and 1.082 g/ml were depleted of cells adherent to plastic tissue culture dishes. The nonadherent cells were further incubated on dishes coated with P55 MoAb. CFU-MK were enriched about 50-fold in the adsorbed cell fraction. This sequential fractionation procedure resulted in a 345-fold (range 276 to 412-fold) enrichment of rat CFU-MK over whole bone marrow cells. The average cloning efficiency of CFU-MK in the final fraction was about 7% (range 5%-9.2%) of the nucleated cells. The overall recovery of CFU-MK averaged 20% (range 9%-29%). The panning step provided a 46-fold enrichment of megakaryocyte burst-forming cells (megakaryocyte burst-forming units, BFU-MK), whose average cloning efficiency in the post-panning fraction was 0.14% (range 0.07%-0.2%). In addition, erythroid burst-forming cells (erythroid burst-forming units, BFU-E) were also significantly enriched by panning, but to a lesser degree than BFU-MK and CFU-MK. By contrast, granulocyte-macrophage colony-forming cells (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid colony-forming cells (erythroid colony-forming units, CFU-E) were not enriched by panning. CFU-MK obtained after panning formed megakaryocyte colonies in the presence of recombinant rat interleukin 3 (rIL-3), mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF), or human erythropoietin (hEPO), as has been reported for murine CFU-MK in whole marrow cells. The highly enriched populations of rat CFU-MK should thus provide a basis for the further study of the regulation of megakaryocytopoiesis.
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PMID:Purification of rat megakaryocyte colony-forming cells using a monoclonal antibody against rat platelet glycoprotein IIb/IIIa. 162 3

Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been shown to be a hematopoietic growth factor that preferentially stimulates the proliferation of immature hematopoietic progenitor cells (HPC). We studied the effect of MGF on the in vitro growth of clonogenic leukemic precursor cells in the presence or absence of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or erythropoietin (EPO). Leukemic blood and bone marrow cells from patients with various types of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) in chronic phase, as well as bone marrow samples from patients with myelodysplastic syndromes (MDS) were studied. MGF as a single factor did not induce significant colony formation by clonogenic leukemic precursor cells. In the presence of IL-3 and/or GM-CSF, MGF weakly stimulated the colony formation by clonogenic precursor cells from patients with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly induced both size and number of leukemic colonies from patients with CML in chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated erythroid colony formation by CML precursor cells. Cytogenetic analysis of the colonies showed that all metaphases after 1 week of culture were derived from the leukemic clone. In patients with MDS, MGF strongly stimulated myeloid colony formation in the presence of IL-3 and/or GM-CSF (up to fourfold), and erythroid colony formation in the presence of EPO (up to eightfold). Not only the number, but also the size of the colonies increased. In the presence of MGF, the percentage of normal metaphases increased in three patients tested after 1 week of culture compared with the initial suspension, suggesting that the normal HPC were preferentially stimulated compared with the preleukemic precursor cells. In the absence of exogenous EPO and in the presence of 10% human AB serum, MGF in the presence of IL-3 and/or GM-CSF induced erythroid colony formation from normal bone marrow and patients with MDS or CML, illustrating that MGF greatly diminished the EPO requirement for erythroid differentiation. These results indicate that MGF may be a candidate as a hematopoietic growth factor to stimulate normal hematopoiesis in patients with acute myeloid leukemia, or with myelodysplastic syndromes.
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PMID:Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic precursor cells. 163 26

A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) by three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride (W-13), and trifluoperazine. Chlorine-deficient analogs of W-7 and W-13, with a lower affinity for calmodulin, did not inhibit the growth of CFU-C colonies. W-7, W-13, and trifluoperazine inhibited the colony formation of immature erythroid progenitor cells (BFU-E) stimulated by IL-3 plus erythropoietin (Ep) or GM-CSF plus Ep, in a dose-dependent manner, while they did not affect the colony formation of mature erythroid progenitor cells (CFU-E) induced by Ep. W-7, W-13, and trifluoperazine also led to a dose-dependent inhibition of GM-CSF-induced colony formation of KG-1 cells. Calmodulin-dependent kinase activity derived from the KG-1 cells was inhibited by these three calmodulin antagonists in a dose-dependent manner. These data suggest that calmodulin may play an important regulatory role via a common process in the growth of hematopoietic progenitor cells stimulated by IL-3, GM-CSF, and G-CSF. Mechanisms related to the growth signal of Ep apparently are not associated with calmodulin-mediated systems.
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PMID:A role for calmodulin in the growth of human hematopoietic progenitor cells. 169 May 78

The pathogenic effects of human cytomegalovirus (CMV) infection in vitro on hematopoiesis were investigated. Normal human bone marrow cells from both seronegative and seropositive donors were challenged with CMV (Towne or wild-type strain) and tested for their responsiveness to the recombinant hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF), respectively. Regardless of the serostatus of the donor, infection with CMV resulted in a significant decrease in the proliferation and colony formation of hematopoietic progenitor cells in response to both growth factors, with more pronounced suppression in response to G-CSF being observed. Evaluation of the colony composition revealed a profound decrease in colonies of the granulocytic (CFU-G), or granulocyte-macrophage (CFU-GM) lineages, while suppression of multipotential (CFU-GEMM) and erythroid (BFU-E) colony-forming cells occurred after infection with wild-type but not the laboratory strain of CMV. Although no evidence of productive virus infection could be seen in colony-forming cells, in situ hybridization studies and immunohistochemical staining revealed the presence of CMV-specific mRNA and immediate-early antigens, demonstrating that a small proportion of cells were abortively infected. These studies demonstrate that CMV can infect bone marrow progenitor cells and interfere with normal hematopoiesis in vitro, which may help to explain the hematologic defects seen during acute infections with CMV in vivo.
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PMID:Preferential suppression of myelopoiesis in normal human bone marrow cells after in vitro challenge with human cytomegalovirus. 169 91

The human multilineage hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) induces multipotent, erythroid, and eosinophil colony formation from highly enriched normal bone marrow cells. We have examined the effects of GM-CSF combined with granulocyte-CSF (G-CSF) or macrophage-CSF (M-CSF) on the monolineage granulocytic, eosinophilic, and macrophage progenitor cells (CFU-G, CFU-Eo, and CFU-M) in accessory cell depleted marrow fractions. GM-CSF effects were assessed in direct comparison with those of interleukin-3 (IL-3) plus G-CSF or M-CSF. GM-CSF strongly synergized with G-CSF in the formation of granulocytic colonies with respect to number and size and enhanced the in vitro survival of CFU-G. More immature cells were present in colonies induced by the mixture of GM-CSF and G-CSF than by G-CSF alone. GM-CSF also synergized with M-CSF in the formation of macrophage colonies (number and size). The addition of G-CSF and M-CSF did not influence eosinophil colony formation induced by GM-CSF or IL-3. Experiments directly comparing GM-CSF and IL-3 revealed that the effects of GM-CSF on G and M colony-forming cells were significantly greater than those of IL-3. The potent positive effects between GM-CSF and G-CSF as well as between GM-CSF and M-CSF provide a powerful mechanism of amplification of granulopoiesis and monocytopoiesis.
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PMID:Synergistic effects between GM-CSF and G-CSF or M-CSF on highly enriched human marrow progenitor cells. 169 8

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