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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)

Granulocyte colony-stimulating factor (G-CSF) is known to act on the neutrophilic granulocytes from chronic myelogenous leukemia (CML) patients to induce neutrophil alkaline phosphatase (NAP) activity. Gamma-interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to suppress NAP induction with G-CSF. We confirmed that this inhibitory effect of GM-CSF is accompanied by the decrease of the NAP mRNA level. Moreover, we found that the simultaneous addition of retinoic acid completely neutralized this inhibitory effect of GM-CSF. Recovery of the NAP activity brought about by the retinoic acid was also accompanied by the increase of NAP mRNA level. These results indicate that retinoic acid neutralizes the inhibitory effect of GM-CSF on the induction of NAP activity through the change of the NAP mRNA level.
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PMID:Retinoic acid acts to neutralize the inhibitory effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on alkaline phosphatase activity of neutrophils that is induced by granulocyte colony-stimulating factor (G-CSF). 137 89

Studies on the effect of the microenvironment on hematopoiesis would benefit from the availability of pure populations of nontransformed cells of each of the stromal cell types. The adherent murine bone marrow stromal cell population in this study consisted of fibroblasts, endothelial cells, and macrophages. Fibroblasts were segregated from the phagocytic endothelial cells and macrophages by allowing the phagocytic cells to ingest magnetic beads, with subsequent exposure to a magnetic field, effecting cell separation. Pure colony cultures of fibroblasts and endothelial cells were formed by varying the bead-to-cell ratio and incubation period of the cells. For complete purification of the fibroblasts, subsequent passaging was also necessary. Near confluent growth of each type was obtained with subsequent passages and sustained culture. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to enhance endothelial cell growth. We were not able to obtain pure populations of bone marrow macrophages in near confluent culture. The three cell types were identified by cellular morphology, acid and alkaline phosphatase staining, binding with the lectins Ulex europaeus and Bandeiraea simplicifolia, and the capacity to stain for the factor VIII-related antigen (von Willebrand's Factor).
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PMID:A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow. 220 58

The effects of recombinant cytokines on the ploidy of human megakaryocytes derived from megakaryocyte progenitors were studied using serum-free agar cultures. Nonadherent and T cell-depleted marrow cells were cultured for 14 days. Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet IIb/IIIa. The ploidy of individual megakaryocytes in colonies was determined by microfluorometry with DAPI (4',6-diamidino-2-phenylindole) staining. Recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner. However, both rhIL-3 and rhGM-CSF had no definite ability to increase the ploidy values. Recombinant human erythropoietin (rhEpo) or recombinant human macrophage colony-stimulating factor (rhM-CSF) by itself did not stimulate the growth of megakaryocyte progenitors. rhEpo or rhM-CSF, however, stimulated increases in the number, size and ploidy values of megakaryocyte colonies in the presence of rhIL-3 or rhGM-CSF. Recombinant human interleukin 6 (rhIL-6) showed no capacity to generate or enhance megakaryocyte colony formation when added to the culture alone or in combination with rhIL-3. rhIL-6, however, increased the ploidy values in colonies when added with rhIL-3. These results show that rhEpo, rhM-CSF and rhIL-6 affect endomitosis and that two factors are required for megakaryocyte development.
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PMID:The effect of cytokines on the ploidy of megakaryocytes. 220 62

Tetranectin, a protein recently identified in a wide variety of human secretory cells (Christensen, L., and I. Clemmensen. 1989. Histochemistry. 92:29-35) was found to colocalize with latent alkaline phosphatase activity in fractions well separated from azurophil granules, specific granules, gelatinase-containing granules, and plasma membranes when postnuclear supernatants of nitrogen-cavitated neutrophils were fractionated on discontinuous Percoll density gradients. Stimulation of intact neutrophils with nanomolar concentrations of FMLP, leukotriene B4, 10-100 U/ml of tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor resulted in parallel release of tetranectin and translocation of alkaline phosphatase to the plasma membrane. Furthermore, intracellular pools of tetranectin and latent alkaline phosphatase were completely released from neutrophils under conditions that barely induced release of specific granules containing B12-binding protein. These findings indicate that tetranectin and latent alkaline phosphatase define an easily mobilizable population of cytoplasmic storage organelles in human neutrophils which are functionally distinguishable from azurophil, specific, and gelatinase-containing granules. These organelles may play an important role as stores of membrane proteins that are mobilized to the cell surface during stimulation by inflammatory mediators.
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PMID:Identification of a highly mobilizable subset of human neutrophil intracellular vesicles that contains tetranectin and latent alkaline phosphatase. 229 16

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.
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PMID:Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones. 240 45

The activity of human osteoblast-like cells cultured in vitro is regulated by a number of factors, which include systemic hormones as well as agents that can be produced locally within bone. Several cytokines and growth factors have been demonstrated to be produced by osteoblasts themselves, and this includes granulocyte-macrophage colony-stimulating factor (GM-CSF). In this report we show that recombinant human GM-CSF (rhGM-CSF) modulates the activities of osteoblast-like cells derived from human trabecular bone in vitro. rhGM-CSF stimulated the proliferation of the cultured human osteoblast-like cells, but antagonised the induction by 1,25(OH)2D3 of osteocalcin synthesis and alkaline phosphatase activity, two characteristic products of osteoblasts. rhGM-CSF however, had no appreciable effect on the production of prostaglandin E2, or on the plasminogen activator activity associated with human osteoblast-like cells. These results are the first report of which we are aware of an apparently direct action of GM-CSF on cells of the osteoblast phenotype. These studies indicate that GM-CSF represents another haematological factor that can potentially exert regulatory actions on human osteoblast-like cells. GM-CSF may therefore be a potential paracrine/autocrine regulator of osteoblast activity.
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PMID:The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on human osteoblast-like cells. 265 92

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

In a patient with Ph1-positive chronic myelogenous leukaemia (CML), the development of a localized blastoma preceding generalized blastic transformation was accompanied by a reduction of granulocyte-macrophage (GM) colony forming capacity in agar of bone marrow cells as well as an increase in peripheral neutrophil alkaline phosphatase (NAP) scores. Successful transplantation of the blastoma cells into nude mice enabled extensive studies of the cell properties. The blastoma cells were double Ph1-positive cells which did not respond to human granulocyte-macrophage colony-stimulating factor (GM-CSF), and were similar to cells demonstrated in spleen and bone marrow at the terminal stage of the patient's illness. These observations clearly support the case for sequential studies of colony formation in vitro as a useful test for the early detection of disturbances in marrow function that may occur before generalized blastic transformation. Studies of the properties of the blastoma cells also provide some insight into possible mechanisms for the transformation event.
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PMID:Localized blastoma preceding blastic transformation in Ph1-positive chronic myelogenous leukaemia: morphological and cultural studies of the transformation event. 693 75

Using postmitotic granulocytes (PMGs) with low neutrophil alkaline phosphatase activity (NAP activity), factor(s) having the capacity to increase their NAP activity were examined in vitro. A high activity of the factor was demonstrated in the cystic fluid of a human squamous cell carcinoma, which is known to produce a large amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). The NAP-stimulating factor increased NAP values both in PMGs from normal bone marrow and PMGs from patients with chronic myeloid leukemia (CML), and NAP values in cells treated with the factor approached or rose above those of normal peripheral granulocytes after 48 hr of culture. The effect of the factor was specific in that the factor caused stimulation only in granulocytic series. These findings may indicate that increases in NAP activity reflect maturation or granulocytes and that low NAP activity of neutrophils derived from patients with CML is due to the immaturity of these cells. The relationship between the factor responsible for the increase in NAP activity and GM-CSF is also discussed.
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PMID:Factor(s) responsible for the increase in alkaline phosphatase activity of postmitotic granulocytes from normal individuals and patients with chronic myeloid leukemia. 697 95

We established a human bone marrow stromal cell line (Saka) by infecting marrow adherent cells from semisolid marrow cultures with a recombinant simian virus-40 (SV40) virus. The cells expressed SV40 large tumor antigen, had a fibroblast-like shape, and expressed fibronectin and vimentin. They did not contain detectable alkaline phosphatase activity; express myeloid, lymphoid, or factor VIII-associated antigens; or develop adipocyte-like characteristics with dexamethasone treatment. Polymerase chain reaction analysis of Saka cell RNA detected expression of messenger RNAs for interleukin-6 (IL-6), IL-1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, and the 1,25-dihydroxyvitamin D3 receptor. Coculture of Saka cells with human marrow mononuclear cells enhanced formation of osteoclast-like multinucleated cells (MNC) in long term human bone marrow cultures. These MNC expressed calcitonin receptors and formed resorption lacunae on dentine. In contrast, coculture of marrow mononuclear cells with other SV40-transformed human marrow stromal cell lines did not increase MNC formation. Conditioned medium from Saka cells or coculture of bone marrow and Saka cells separated by a Millipore membrane did not enhance MNC formation. Addition of a neutralizing antibody to IL-6 or IL-1 beta blocked the effects of Saka cells on MNC formation. These results suggest that marrow stromal cells enhance osteoclast formation in part through direct cell to cell contact and production of IL-6 and/or IL-1 beta.
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PMID:Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. 753 99


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