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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)

Research in recombinant DNA technology has led to the characterization of colony-stimulating factors (CSFs) as a family of glycoprotein hormones that are thought to regulate blood cell proliferation and differentiation. CSFs also have been studied for their potential use in treating various hematologic, infectious, and neoplastic disorders. Preliminary-results using granulocyte-macrophage colony-stimulating factor to restore leukocyte competence in acquired immune deficiency syndrome and myelodysplastic syndrome patients have been impressive. Toxic effects generally have not been severe. Other hematopoietic factors are receiving scrutiny for their potential clinical applications.
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PMID:Colony-stimulating factors: present status and future applications. 305 7

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.
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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.
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PMID:Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. 305 4

For direct studies of growth control, a method was developed to purify viable human megakaryocytes to homogeneity from routine normal bone marrow aspirates. An initial separation of marrow over a 1.050 g/mL Percoll density cut was used to enrich megakaryocytes. After washing, the cells were specifically labeled with a fluoresceinated monoclonal antibody or F(ab')2 fragment to the platelet glycoprotein (GP) IIb/IIIa complex. Megakaryocytes were selectively sorted by using Becton Dickinson FACStar flow cytometer on the basis of a fluorescence intensity greater than 50-fold that of control cells. To increase resolution and purity the sorting rate was adjusted to one cell in 13 formed drops, and negative events that coincided with positive ones were aborted. Two thirds of the isolated cells were large, morphologically recognizable megakaryocytes with a forward light scatter fourfold that of the main cell population. Microscopic examination showed these cells to be greater than or equal to 98% megakaryocytes with a diameter of 20 to 46 microns and a ploidy range of 2N to 64N with a mode of 16N. The small highly fluorescent cells were 10 to 21 microns in diameter, and their ploidy range from 2N to 32N with main ploidy classes of 2N and 4N. The majority of these small cells also positively reacted with monoclonal antibody to platelet GPIb. The isolated cells were cultured in either Iscove's or leucine, lysine-deficient RPMI 1640 medium with 10% human plasma. The cells were maintained in culture more than three days and were capable of synthesis of both DNA and protein as assessed by radiolabeled thymidine and amino acid incorporation. Moreover, the isolated megakaryocytes were capable of responding to recombinant granulocyte-macrophage colony-stimulating factor. The data show that human megakaryocytes can be purified from routine marrow aspirates on the basis of a lineage marker and that they are capable of growth in vitro.
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PMID:Purification of human megakaryocytes by fluorescence-activated cell sorting. 331 39

Colony-stimulating factors (CSFs) are glycoproteins that stimulate the growth of hematopoietic progenitors and enhance the functional activity of mature effector cells. Human granulocyte/macrophage colony-stimulating factor (GM-CSF) is a 22-kDa glycoprotein that stimulates the growth of myeloid and erythroid progenitors in vitro and increases the responsiveness of neutrophils, monocytes, and eosinophils to physiologic stimuli. Elucidation of the cell and tissue sources of CSFs, as well as study of their regulation of expression, is required to understand their role in physiologic and pathophysiologic states. An extensive survey of normal and neoplastic human tissues did not reveal constitutive production of detectable levels of GM-CSF mRNA in any of the 64 samples studied. Antigen- or lectin-activated T lymphocytes have been shown to produce GM-CSF; therefore, to elucidate the genetic sequences required, we constructed recombinant plasmids containing 5' flanking DNA of the GM-CSF gene linked to the marker chloramphenicol acetyltransferase gene. The recombinant constructs were transfected into a human T-cell leukemia virus type I (HTLV)-infected T-lymphoblast cell line that can be stimulated to produce high levels of GM-CSF. We show here that the 5' flanking sequences of the GM-CSF gene can direct increased expression of the chloramphenicol acetyltransferase gene in activated T-lymphoblast cells.
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PMID:Regulation of expression of human granulocyte/macrophage colony-stimulating factor. 349 Jun 69

A factor, termed neutrophil alkaline phosphatase-inducing factor (NAP-IF), that has the capacity to increase the NAP activity of granulocytes was characterized by using two samples: cystic fluid (CF) and conditioned medium of a tumor cell line (T3M5). The molecular weight of NAP-IF was shown to be between 13,000 and 45,000, and its isoelectric point was between 5.5 and 6.2. It was sensitive to heat and proteolytic enzymes, but was resistant to DNase and RNase, suggesting that NAP-IF is an acidic protein or glycoprotein. These characteristics of NAP-IF seem to be similar to those of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is also present in the CF. NAP-IF rich fractions obtained by isoelectric focusing from CF were also found to be rich in a subclass of GM-CSF: granulocyte-CSF (G-CSF). Furthermore, a high correlation was noted between the activities of G-CSF and NAP-IF (gamma = 0.798, P less than 0.005). These results suggest that the two activities, i.e., G-CSF and NAP-IF, may be attributable to an identical macromolecule.
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PMID:Characterization of neutrophil alkaline phosphatase-inducing factor (NAP-IF). 387 40

Some biological and biochemical properties of a distinct hemopoietic factor that stimulates splenic hemopoiesis in mice are described. This factor can be detected by measuring the increase in the number of in vitro hemopoietic colony-forming cells (CFCs) in the spleens of mice after transfer of serum from syngeneic donors that have been treated previously with the bacterial cell-wall components: lipid A or lipoprotein. Serum collected 5 min after the IV injection of lipid A contained almost no splenic hemopoiesis-stimulating factor (SHSF). The highest serum levels of the factor were found between 30 min and 3 h after lipid A was injected IV. The residual levels of lipid A or lipoprotein in the serum of treated mice were too low to account for their splenic hemopoiesis-stimulating effects. A component of SHSF in both post-lipid-A serum (PLAS) and postlipoprotein serum (PLPS) bound to concanavalin A (Con A)-Sepharose and could be eluted by alpha-methyglucopyranoside (0.05 M). Partial fractionation of PLAS using Con A-Sepharose and gel filtration (Sephacryl S-200) indicated that the SHSF glycoprotein had an apparent molecular weight of 30,000 daltons. SHSF was detected in serum in response to lipid A and lipoprotein, but this was separable (by gel filtration) from the major form of granulocyte-macrophage colony-stimulating factor (GM-CSF) in PLAS.
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PMID:Biological and biochemical properties of a serum factor that stimulates splenic hemopoiesis in mice. 660 44

We have examined the biologic and physical properties of a human T-lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.
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PMID:Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor. 696 9

A new and quantitative liquid culture system has been developed to measure the production of megakaryocytes from megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]). The system uses as a target population a glycoprotein (Gp) IIb/IIIa+ subpopulation of rat bone marrow cells previously demonstrated to be highly enriched for CFU-MK. GpIIb/IIIa+ cells were cultured at 5 x 10(4) cells/mL (10(4) cells/well) with test samples in 96-well tissue culture plates for 4 days at 37 degrees C. During the final 3 hours of incubation, the cells were pulsed with [14C]5-hydroxytryptamine creatinine sulfate (14C-serotonin). After incubation, the plates were washed and the cell pellets were lysed with Triton-X 100. The cell lysate was infiltrated into a commercially available solid scintillator and dried, and radioactivity was measured. In this assay system, rat interleukin-3 (IL-3) was found to be the most potent among known cytokines tested. Murine granulocyte-macrophage colony-stimulating factor (GM-CSF), human erythropoietin (Epo), human IL-6, and murine stem cell factor (SCF) each alone stimulated megakaryocyte growth but were much less active than rat IL-3. Plasma of rats rendered thrombocytopenic by injection of monoclonal antirat platelet GpIIb/IIIa antibody exhibited significant activity, and the active protein fractions partially purified from the plasma showed much higher activity, but normal rat plasma had no effect. This liquid culture system allows the measurement of a large number of test samples--including a wide variety of cytokines and unknown growth factors, alone or in combinations--and provides a simple method for evaluating the early proliferative events involving CFU-MK in the megakaryocyte differentiation pathway.
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PMID:A simple and quantitative liquid culture system to measure megakaryocyte growth using highly purified CFU-MK. 755 34

Protracted thrombocytopenia and bleeding remain serious complications in bone marrow transplantation (BMT). Major progress has been made in facilitating myeloid and erythroid engraftment, but little has been made in accelerating thrombopoiesis post-BMT. We report that in vitro preincubation of T cell-depleted BM allografts with a combination of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 microgram/mL each) (n = 8), for 3 days prior to infusion, expands megakaryocyte (MK) precursors. MK-progenitor proliferation was assessed in plasma clot colony assays and liquid cultures following pre-exposure to IL-3/GM-CSF. We observed a 2.8-fold increase in the number of colony-forming units-megakaryocyte (CFU-MK) (17.3 +/- 5.2 vs. 6.1 +/- 3.4) (p = 0.001) and a two-fold increase in burst-forming units-megakaryocyte (BFU-MK) (0.2 vs. 0.1) (p = 0.01) per 2 x 10(5) cells/mL compared to control BM samples cultured for 3 days in medium alone. In secondary cultures, the continued presence of IL-3 and GM-CSF increased the number of CFU-MK by 200-fold (p < 0.0001) over controls and by 9.7-fold over fresh BM. A 33-fold increase (p < 0.0001) in the number of BFU-MK was elicited compared to controls. In addition, IL-3 plus GM-CSF supported increased cellularity within the colonies. The presence of IL-3 or GM-CSF alone resulted in fewer MK colonies and fewer cells per colony than both cytokines combined. In liquid cultures, the percentage of cells expressing platelet glycoprotein (GP) IIb/IIIa in the continued presence of IL-3 and GM-CSF increased following preincubation, yielding a total of 16.0 +/- 2.3 x 10(4) MK/2 x 10(6) cells at day 10 of culture. We propose that ex vivo preincubation with IL-3 and GM-CSF can expand the number of MK precursors and may facilitate platelet recovery post-BMT.
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PMID:Ex vivo expansion of megakaryocyte precursors by preincubation of marrow allografts with interleukin-3 and granulocyte-macrophage colony-stimulating factor in vitro. 758 81


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