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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)

Aplastic anemia serum (AAS) contains humoral factors that alter both proliferation and maturation of human megakaryocytes (MK). The ability of AAS to augment MK colony formation (colony-forming unit, CFU-MK) was neutralized by an antiserum against MK colony-stimulating factor (MK-CSF), a glycoprotein isolated from AAS. The adsorbed AAS still retained the ability to accelerate cytoplasmic maturation of recognizable MK. Similar experiments were done with thrombocytopoiesis-stimulating factor (TSF) and an anti-TSF antiserum to further define the activity in AAS responsible for accelerating cytoplasmic maturation. Bone marrow fractions enriched for recognizable human MK, but devoid of CFU-MK, were obtained by centrifugal elutriation and placed in short-term liquid cultures. MK progressed through identifiable maturation stages (1-4) more quickly in the presence of either TSF or AAS. TSF slightly enhanced the cloning efficiencies of CFU-MK, but did not alter the number of MK in individual colonies derived from non-adherent, low-density, T-cell-depleted bone marrow. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and crude AAS substantially augmented both MK colony formation and cells per colony. TSF also doubled the percent 35S incorporation into platelets of immunothrombocythemic mice, but stimulation was completely abolished by anti-TSF. Anti-TSF antiserum was then used to analyze the promotion of MK colony formation by cytokines. Cloning efficiencies of CFU-MK were reduced to baseline values when TSF was pretreated with anti-TSF; however, the MK colony-stimulating activity (MK-CSA) of GM-CSF, IL-3, or AAS was not altered by adsorption with anti-TSF. In contrast, the cytoplasmic maturation of recognizable MK was slower, and fewer mature stage-4 cells were present at days 1-3 in AAS adsorbed with anti-TSF than MK cultured in AAS treated with normal rabbit serum or untreated AAS. Therefore, TSF appears to be a major factor in AAS that accelerates terminal maturation of human MK. TSF primarily affects megakaryocytopoiesis by promoting MK maturation rather than enhancing CFU-MK proliferation.
Exp Hematol 1989 Dec
PMID:Effects of thrombocytopoiesis-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes. 268 80

Because inflammatory processes in renal glomeruli may involve monocyte-macrophages (MPs) and T-lymphocytes, we have investigated whether products of glomerular mesangial cells (MCs) can stimulate the proliferative activity of these effector cells. We found that cultured rat MCs (subcultures 2-15), maintained under serum-free conditions, secrete a soluble factor into the supernate [MC-conditioned medium (CM)], which supports growth of the T-helper cell-derived line HT-2. Moreover, MC-CM increased [3H]thymidine incorporation by thioglycollate-elicited peritoneal MPs but did not induce growth of the interleukin 2 (IL-2)- or interleukin 4 (IL-4)-dependent cell line CTLL-2. Further functional, serological, and biochemical analysis of MC-CM revealed that rat MCs secrete a cytokine that, by all of the techniques used, is indistinguishable from granulocyte-macrophage colony-stimulating factor (GM-CSF). Both northern blot and in situ hybridization with a specific cDNA probe for murine GM-CSF showed that MCs express GM-CSF mRNA transcripts. The present findings indicate that cultured rat MCs produce GM-CSF. Release of GM-CSF by MCs in vivo may play a role in the interaction of MCs with MPs, T-cells, and neutrophils in glomerular disease.
Am J Physiol 1989 Dec
PMID:Rat mesangial cells produce granulocyte-macrophage colony-stimulating factor. 269 Jun 41

Osteoblasts play a central role in the regulation of bone remodeling. Not only are they responsible for the formation of new bone, but they also regulate bone resorption. These cells also exert regulatory influences outside the bone in that they are able to regulate hematopoiesis. However, obtaining pure populations of osteoblasts devoid of contaminating cell types remains problematic. One approach to this problem is the use of cloned osteoblastic cell lines. To this end we have used MC3T3-E1, a cloned murine osteoblast cell line of C57BL/6 origin. We report that MC3T3-E1 cells respond to lipopolysaccharide (LPS) and, to a lesser extent, parathyroid hormone (PTH) by the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). However, 1,25-(OH)2D3, a potent activator of osteoblasts, fails to induce these cells to secrete GM-CSF. These results suggest that MC3T3-E1 cells respond to osteotropic agents in a hierarchical fashion. Secretion of GM-CSF is not constitutive but rather requires active induction of the cells. MC3T3 cells fail to secrete detectable levels of interleukin-2 (IL-2), IL-3, or IL-4, regardless of whether or not the cells are activated. The data indicate that MC3T3-E1 cells secrete cytokines in response to osteotropic agents in a way similar to that of normal primary osteoblasts. Therefore, MC3T3-E1 cells may serve as a good in vitro model for primary osteoblasts.
J Bone Miner Res 1989 Dec
PMID:Osteotropic agents induce the differential secretion of granulocyte-macrophage colony-stimulating factor by the osteoblast cell line MC3T3-E1. 269 6

Both interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce increased histamine production by murine hemopoietic cells. Histidine-free culture conditions or addition of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, completely abrogate this phenomenon, indicating that increased histamine levels result from an augmentation of the rate of its synthesis. L-Histidine decarboxylase (HDC) (EC 4.1.1.22) activity is detected in normal bone marrow cell lysates. It is markedly increased following incubation of the cells with IL-3 or GM-CSF. The cells responding by the most important enhancement of HDC activity are located in the less dense layers of a discontinuous Ficoll gradient containing the majority of the hemopoietic progenitor cell types, such as colony-forming units (spleen), granulocyte-macrophage colony-forming cells, and mast cell precursors. In comparison with other HDC-containing cell populations tested, the enzymatic activity contained in these cells is particularly high after IL-3 or GM-CSF treatment and similar to the HDC levels observed in murine fetal liver. The time course of IL-3 and GM-CSF-induced HDC activation at comparable concentrations is slightly different. In response to GM-CSF, HDC activation is more rapid, with a significant enhancement after 4 hr of incubation, as compared with IL-3-induced HDC activation. Moreover, in the latter case the activation increases more progressively up to 48 hr of incubation, whereas GM-CSF-induced increase of HDC activity reaches a plateau more rapidly. In addition, maximal increase in histamine production in response to IL-3 is always higher than in response to GM-CSF. Moreover, the simultaneous presence of both factors at optimal concentration induces only a partially cumulative effect. These results suggest that IL-3 and GM-CSF induce HDC activation in two distinct ways, possibly reflecting the involvement of distinct target cells. However, both mediators act by inducing the transcription of the HDC gene and de novo synthesis of this enzyme since actinomycin D or cycloheximide abolish GM-CSF-or IL-3-induced histamine-producing cell-stimulating activity. This synthesis is independent from cell proliferation as demonstrated by the lack of effect of bone marrow cell irradiation. Finally, the observation that cholera toxin, prostaglandin E2, and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate mimic the effects of IL-3 and GM-CSF on bone marrow cell HDC suggests an involvement of cyclic adenosine monophosphate in factor-induced histamine-producing cell-stimulating activity.
J Immunol 1987 Dec 01
PMID:Histamine-producing cell-stimulating activity. Interleukin 3 and granulocyte-macrophage colony-stimulating factor induce de novo synthesis of histidine decarboxylase in hemopoietic progenitor cells. 282 13

Colony-stimulating factor-1 (CSF-1) is a specific haematopoietic growth factor that stimulates the production of macrophages by both bone marrow macrophage precursors (GM-CFC) and certain more mature peripheral tissue macrophages. The relationship of CSF-1 utilization and cell production by macrophage precursors at various stages of differentiation was studied. Bone marrow GM-CFC had the highest proliferative capacity followed by blood monocytes and peritoneal exudate macrophages (PEM) as determined by their cell doubling time (DT) which was also dependent on the concentrations of exogenous CSF-1. PEM had the longest initial lag period before commencing cell proliferation. Exogenous CSF-1 was constantly utilized by the growing cells; depletion of available CSF-1 resulted in growth arrest and, subsequently, cell death. The production of macrophage progeny, per amount of CSF-1, correlated with parent macrophage maturity; for each 100 U of CSF-1 consumed, bone marrow precursor cells and blood monocytes were capable of producing 17.9 x 10(4) and 13.4 x 10(4) progeny, respectively, whereas PEM generated only 4.6 x 10(4) daughter cells. Thus, the removal and destruction of CSF-1 by more mature, less proliferative tissue macrophages may provide a possible mechanism by which CSF-1 levels are reduced and the production of early haemopoietic macrophage precursors controlled.
Br J Haematol 1987 Dec
PMID:Delineation of receptor-mediated colony-stimulating factor (CSF-1) utilization and cell production by precursors of mononuclear phagocytic series at various stages of differentiation. 282 20

Activation of T cells by an antigen, a mitogen, or a combination of a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) leads to induction of a set of lymphokine genes. Treatment of human T-cell leukemia line Jurkat by a mitogen or p40x, a transactivator protein encoded by human T-cell leukemia virus type I, activates many transfected lymphokine genes in a transient transfection assay. To study the mechanism of lymphokine gene induction, we examined the effects of mitogen stimulation and p40x on the gene for the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) in Jurkat cells. Deletion and mutation analyses showed that the 5'-flanking region of the gene for the GM-CSF is composed of two types of regulatory elements. One sequence, located at positions -95 to -73, determines response to stimulation by either TPA-A23187 or p40x. This region contains conserved lymphokine element 2, which appears in the gene for interleukin 3 (IL-3) and is followed by a GC-rich stretch. This GC-rich stretch alone specifies inducible response to p40x but not to TPA-A23187. Another sequence, located at positions -113 to -96 upstream of a TATA-like sequence, mediates inducible response to p40x but not to TPA-A23187. This sequence includes conserved lymphokine element 1, which appears in several lymphokine-cytokine genes, such as those for IL-3, G-CSF, and IL-2. We previously showed that the simian virus 40 early region promoter was also induced by a mitogen or p40x in Jurkat cells. Deletion analysis showed that the minimum region require for stimulation by both signals are identical. These results, which indicate that p40(x) stimulates transcription of the gene for the GM-CSF or the simian virus 40 early region promoter through the same DNA element or an overlapping DNA element required for induction by a mitogen, lend further support to the notion that p40(x) can exert its function by activating a component(s) of the T-cell signal transduction pathway which is activated by an antigen or a mitogen.
Mol Cell Biol 1988 Dec
PMID:T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. 285 2

Supernatants from a subset of helper T cell clones can enhance IgA, IgE, and IgG1 production in cultures of lipopolysaccharide-stimulated, T cell-depleted spleen cells. The lymphokine interleukin (IL)-4 has been shown to cause the IgE and IgG1 enhancement produced by these supernatants. IgA enhancement, however, is mediated by a factor distinct from IL-4, although IL-4 can potentiate the effect of the IgA-enhancing factor. IgA-enhancing factor is also distinct from IL-1, IL-2, IL-3, granulocyte-macrophage colony-stimulating factor, and interferon-gamma and acts directly on B cells. Purified IgA-enhancing factor enhances IgA production three- to sixfold yet causes less than a twofold increase in other isotypes. The IgA enhancing activity is not inhibited by concentrations of interferon-gamma that inhibit IL-4 activities. In the accompanying article, we show that this IgA enhancing activity is a novel property of the lymphokine IL-5.
J Immunol 1987 Dec 01
PMID:A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. 296 Jul 39

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 22,000-dalton glycoprotein that stimulates the growth of myeloid progenitor cells and acts directly on mature neutrophils. A full-length complementary DNA clone encoding human GM-CSF was used as a probe to screen a human genomic library and isolate the gene encoding human GM-CSF. The human GM-CSF gene is approximately 2.5 kilobase pairs in length with at least three intervening sequences. The GM-CSF gene was localized by somatic cell hybrid analysis and in situ hybridization to human chromosome region 5q21-5q32, which is involved in interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. An established, human promyelocytic leukemia cell line, HL60, contains a rearranged, partially deleted GM-CSF allele and a candidate 5q- marker chromosome, indicating that the truncated GM-CSF allele may reside at the rejoining point for the interstitial deletion on the HL60 marker chromosome.
Science 1985 Dec 13
PMID:The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly. 299 78

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein hormone that stimulates the growth of hematopoietic progenitor cells and enhances the functional activity of mature myeloid effector cells. Granulocyte-macrophage colony-stimulating factor was administered to eight patients with severe aplastic anemia in an attempt to restore adequate hematopoiesis. Profound decreases in serum cholesterol concentrations were observed during GM-CSF therapy that were not dependent on changes in the patients' peripheral blood cell counts. Serum cholesterol levels decreased by an average of 37% during treatment, reaching levels of less than 4.40 mmol/L in all patients. Serum cholesterol concentrations returned to baseline in all patients after discontinuation of GM-CSF therapy. Treatment with GM-CSF prominently alters cholesterol homeostasis in vivo, although the mechanism of this effect is unknown. Our results suggest that GM-CSF may be potentially useful in the treatment of hypercholesterolemia and, possibly, in the prevention and treatment of atherosclerosis.
JAMA 1988 Dec 09
PMID:Serum cholesterol-lowering activity of granulocyte-macrophage colony-stimulating factor. 264 96

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of a family of glycoprotein hormones that stimulate the proliferation and differentiation of hemopoietic cells in vitro and in vivo. We now report that human GM-CSF can also stimulate the proliferation of two osteogenic sarcoma cell lines, a breast carcinoma cell line, a simian virus 40-transformed marrow stromal cell line, and normal marrow fibroblast precursors. These findings suggest a more general regulatory function of GM-CSF on nonhemopoietic cell types than previously anticipated. They also raise the possibility of adverse side effects of GM-CSF therapy in patients whose malignant cells may be directly stimulated by this molecule and suggest a previously unanticipated role of GM-CSF gene activation in the evolution of solid tumors and in the pathogenesis of myelofibrosis.
Proc Natl Acad Sci U S A 1988 Dec
PMID:Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. 305 4


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