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)

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been described as a multi-lineage growth factor that induces in vitro colony formation of bone marrow erythroid burst-forming units (BFU-E), multipotential colony-forming units (CFU-GEMM), granulocyte-macrophage CFU (CFU-GM), granulocyte CFU (CFU-G), macrophage CFU (CFU-M), as well as eosinophil colony-forming units (CFU-Eo). Because of the preeminent role of the liver in fetal hematopoiesis, the effect of human recombinant GM-CSF (hrGM-CSF) on hematopoietic cells isolated from human fetal liver was tested in liquid cultures and in semisolid colony assays. hrGM-CSF induced a significant increase in the number of mature eosinophils in liquid culture and to a lesser extent in semisolid cultures when compared to untreated culture controls. The kinetics of this effect on eosinophils reached its peak on day 21 of culture. When GM-CSF and erythropoietin (Ep) were added simultaneously to the cultures, no significant change in the number of eosinophils compared to hrGM-CSF alone was observed. Ep or granulocyte colony-stimulating factor (G-CSF) did not show any CFU-Eo activity when added separately or simultaneously to both liquid and semisolid cultures. These results indicate that hrGM-CSF alone may be a potent stimulating factor for CFU-Eo obtained from human fetal liver and, in combination with other growth factors, control optimal development of human fetal eosinophils.
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PMID:GM-CSF induces eosinophilic cell growth-promoting activity on human fetal liver cells. 152 2

Natural suppressor (NS) activity has been identified in several sites of active hematopoiesis. In this study we characterized NS activity in murine bone marrow (BM) using monoclonal antibodies (mAbs) to interleukin 3 (IL-3) receptor-associated antigen (IL-3RAA) and various cytokines that exert a strong influence on hematopoiesis or lymphocyte interaction. NS activity of BM cells of relatively low density was enhanced by IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). When the BM cells were separated into IL-3RAA+ cells and IL-3RAA- cells, the IL-3RAA+ cells demonstrated potent NS activity, whereas IL-3RAA- cells had either no or weak NS activity. The IL-3RAA+ cells showed non-T- and non-B-cell phenotype and had high affinity to wheat germ agglutinin (WGA), a marker for hematopoietic progenitors. In assays for hematopoietic activity, it appeared that the early differentiating progenitors (day 8 spleen colony-forming units [CFU-S], granulocyte-macrophage colony-forming units [CFU-GM]) were enriched in the IL-3RAA+ cell population, whereas more immature multipotent progenitors (day 12 CFU-S, granulocyte erythrocyte macrophage megakaryocyte colony-forming units [CFU-GEMM]) were contained in the IL-3RAA- cell population. Both suppressor cells and IL-3RAA+ cells spontaneously developed from the IL-3RAA- cell population. These findings suggest that NS cells in murine BM are early hematopoietic progenitors and are probably committed to the myeloid lineage. Hybridoma cells established between the IL-3RAA+ cells and BW5147 cells produced suppressor factor(s). This finding suggests that the NS cells produce soluble mediator(s) that may be responsible for their suppressive action.
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PMID:Enrichment of murine bone marrow natural suppressor activity in the fraction of hematopoietic progenitors with interleukin 3 receptor-associated antigen. 153 58

Injection of mice with either natural bovine bone-derived or human recombinant transforming growth factor beta 1 (TGF-beta 1) resulted in a significant increase of the macrophage and macrophage-granulocyte-forming capacity of their macrophage colony-stimulating factor (M-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow precursor cells. The increased potential for generating granulocytes and/or macrophages from bone marrow cells of mice injected with TGF-beta 1 was associated with an increase of the number of M-CSF- and GM-CSF-dependent bone marrow colony-forming units (CFU). The effect was selective, in that in vivo applied TGF-beta 1 did not affect interleukin 3 (IL-3)-dependent CFU. The data suggest that TGF-beta may be useful in recovery of bone marrow granulocyte- and macrophage-forming potentials following depletion caused by chemo- or radiotherapy.
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PMID:In vivo regulation of hemopoiesis by transforming growth factor beta 1: stimulation of GM-CSF- and M-CSF-dependent murine bone marrow precursors. 156 60

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

Accumulation of basophils in inflammatory sites is an important aspect of the late-phase allergic reaction involving skin and upper and lower airways, suggesting the existence of mechanisms for basophil migration. Because haemopoietic growth factors have been shown to stimulate various functions of human basophils, we tested the ability of haemopoietic growth factors to migrate basophils in vitro. Both IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced migration of purified normal basophils (purity c. 80%) in a dose-dependent fashion at picomolar concentrations, while granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no effect at all. Chequerboard analyses indicate that migratory activity of both factors are chemokinetic. These results suggest that local production of both factors during allergic reactions might potentially play an initial role in the recruitment of basophils from the circulation to sites of inflammatory reactions.
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PMID:Haemopoietic growth factors induce human basophil migration in vitro. 158 77

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

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

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

Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit-granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation.
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PMID:Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line. 161 65

The lymphokine interleukin-3 (IL-3) promotes the growth and survival of immature hematopoietic cells. Previous studies have shown that IL-3 induces rapid increases in protein-tyrosine kinase (PTK) activity in IL-3--dependent cells. Unlike some other hematopoietic growth factor receptors (eg, c-fms and c-kit), however, the known subunits of the IL-3 receptor (IL-3R) lack intrinsic kinase activity. Recently, it was reported that the IL-2R (whose p75 beta-subunit shares sequence homology with a known murine IL-3R subunit and a common beta-subunit of the human IL-3R and granulocyte-macrophage colony-stimulating factor [GM-CSF] receptors) can physically associate with and regulate the activity of the SRC-family PTK, p56-LCK. Because most IL-3--dependent cells contain p53/56-LYN, but not p56-LCK, we explored the effects of IL-3 on the activities of LYN and other SRC-like PTKs in two human leukemic cell lines, AML-193 and TALL-101, which are phenotypically myeloid, and whose in vitro growth is dependent on IL-3. These cells expressed four of the eight known SRC-family proto-oncogenes: lyn, fyn, yes, and hck. When these factor-dependent leukemic cell lines were deprived of lymphokine to achieve cellular quiescence and then restimulated with IL-3, rapid increases (detectable within 1 minute and maximal by 10 minutes) were observed in the activity of the p53/56-LYN kinase, as assessed by in vitro kinase assays. In contrast, no alteration in the activities of other SRC-family PTKs present in these cells was detected after restimulation with IL-3 under the same conditions. This effect of IL-3 reflected an increase in the specific activity of the LYN kinase, because levels of the 53-Kd and 56-Kd LYN proteins were unaltered by IL-3 stimulation, as assessed by immunoblotting. Furthermore, the magnitude of these inducible increases in LYN kinase activity was dependent on the concentration of IL-3, and correlated with IL-3--induced proliferation. The IL-3--induced upregulation of LYN kinase activity may be mediated by the 120-Kd common subunit of the human IL-3 and GM-CSF receptors, because GM-CSF also stimulated marked increases in the activity of the LYN kinase, whereas granulocyte-CSF (G-CSF) did not, despite inducing cellular proliferation. These observations provide the first example of an IL-3--regulable PTK, and strongly suggest that the p53/56-LYN kinase participates in early IL-3--initiated signalling events, at least in some human leukemic cell lines.
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PMID:Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines. 163 19


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