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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)

We have modified a limiting dilution liquid culture assay, used to quantify hematopoietic progenitor frequency, to simultaneously assess cellular proliferation and differentiation. The frequency of colonies from cord blood obtained with recombinant human interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination was comparable to cultures with IL-3 alone. However, IL-3 and GM-CSF in combination were synergistic for higher granulocyte proliferation than IL-3 alone, indicating that enhanced granulocyte production occurred via action of GM-CSF on progenitor cell populations already stimulated into proliferation by IL-3. Peak proliferation was evident at 4 weeks in culture, with metamyelocytes predominating; at 6 weeks, mostly neutrophils and eosinophils were present, and eosinophils were more numerous in cultures with IL-3. Increasing concentrations of erythropoietin (epo) in liquid culture with IL-3 or GM-CSF decreased absolute granulocyte yield while stimulating erythroid proliferation. The influence of epo on lineage morphology for cells plated in methylcellulose was markedly less evident by comparison, arguing against an inductive effect of epo to shift progenitor cell lineage. This liquid culture methodology may be a useful tool for preclinical screening of cytokines on human hematopoietic progenitor cells.
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PMID:Hematopoiesis in limiting dilution cultures: influence of cytokines on human hematopoietic progenitor cells. 220 54

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

Methodology has been developed that enables virtually complete purification and abundant recovery of early hematopoietic progenitors from normal human adult peripheral blood. A fraction of the pure progenitors is multipotent (generates mixed colonies) and exhibits self-renewal capacity (gives rise to blast cell colonies). This methodology provides a fundamental tool for basic and clinical studies on hematopoiesis. Optimal in vitro cloning of virtually pure progenitors requires not only the stimulatory effect of interleukin-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin, but also the permissive action of basic fibroblast growth factor. These findings suggest a regulatory role for this growth factor in early hematopoiesis.
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PMID:"Pure" human hematopoietic progenitors: permissive action of basic fibroblast growth factor. 221 97

In this report, the biological properties of human recombinant interleukin-3 (rhIL-3) were studied. We investigated the range of unfractionated, purified and single cell human progenitors responsive to IL-3; compared the colony types observed with those obtained in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). The results show that IL-3 directly stimulates the formation of colonies derived from eosinophil and, to a lesser degree, granulocyte and macrophage progenitors. In combination with erythropoietin, it supports the development of erythroid and mixed-erythroid colonies. Furthermore, the data show that IL-3 is a more potent stimulus for both erythroid and eosinophil progenitors than GM-CSF. Interleukin-3 stimulates the formation of both compact and dispersed colonies derived from eosinophil progenitors, whereas GM-CSF stimulates the formation of only the compact type. We conclude that some of the proliferative effects of IL-3 observed on unfractionated and semipurified bone marrow populations are indirect and most likely involve accessory cell interactions.
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PMID:Proliferative properties of unfractionated, purified, and single cell human progenitor populations stimulated by recombinant human interleukin-3. 229 98

Platelet-derived growth factor (PDGF) is an important serum regulator of erythropoiesis in vitro. We have now obtained evidence suggesting that PDGF-like molecules may also modulate erythropoiesis in vivo. Western blot analysis of cytoplasmic extracts from Rauscher murine erythroleukemia cells and phenylhydrazine-treated mouse splenic erythroid cells revealed the presence of several PDGF-like proteins. The presence of PDGF-like proteins in the cytoplasm of these two erythroid cell types was confirmed by immunohistochemical staining. Using a serum-free biologic assay, PDGF-like biological activity was found in cell lysates and conditioned medium of both Rauscher cells and phenylhydrazine-treated mouse erythroid cells. Subcellular localization experiments revealed the biological activity to be concentrated in the cytosolic fraction. Using a series of antibodies to hematopoietic growth factors we demonstrated that PDGF-like biological activity was specifically immunoprecipitated by both monoclonal and polyclonal anti-human PDGF antibodies but not by antibodies to burst-promoting activity, granulocyte-macrophage colony-stimulating factor, IL-3, or erythropoietin. Taken together, the data are consistent with the hypothesis that PDGF-like molecules play a role in the regulation of mammalian erythropoiesis in vivo.
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PMID:Characterization of biologically active, platelet-derived growth factor-like molecules produced by murine erythroid cells in vitro and in vivo. 229 3

The immunological and biochemical characteristics of murine megakaryocyte potentiator from lung and bone marrow were examined and compared with thrombopoietic stimulatory factor. Biological activity was not neutralized by anti-erythropoietin, but megakaryocyte potentiator activity from all three sources was abolished or reduced when the preparations were treated with anti-thrombopoietic stimulatory factor or anti-interleukin-6. Megakaryocyte potentiator levels in lung conditioned medium were not found to be enhanced from mice treated with lipopolysaccharide, in contrast to granulocyte-macrophage colony-stimulating factor (GM-CSF) levels. The biochemical properties of murine megakaryocyte potentiator from lung and bone marrow were compared and found to be similar in the elution profiles from anion exchange, gel filtration and reversed phase liquid chromatography. It is concluded that the activities in lung and bone marrow are very similar if not identical, to interleukin-6.
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PMID:Tissue sources of murine megakaryocyte potentiator: biochemical and immunological studies. 238 66

Human erythroid burst-promoting activity (BPA) of recombinant growth factors and crude materials, of media conditioned by omentum tissue (OMCM), and of media conditioned by the bladder carcinoma cell line (HTB9CM) was measured by three different culture methods. Using the two-stage culture method, significant activity was shown in OMCM (137%-329% of the control), HTB9CM (102%-333%), recombinant human (rh) granulocyte-macrophage colony-stimulating factor (rhGM-CSF) (179%-220%), rh interleukin 3 (rhIL-3) (232%-676%), and rh insulin-like growth factor 1 (rh IGF-1) (106%-175%), whereas there was no significant increase in the number of erythroid bursts by the same additives when the one-stage culture or the delayed erythropoietin method was employed. Linear dose-response curves were observed in the tested range of rhIL-3 and rhGM-CSF. We also observed that 1) a larger amount of rhGM-CSF was required for the optimal stimulation of erythroid burst-forming units (BFU-E) than for the optimal stimulation of granulocyte-macrophage colony-forming units (CFU-GM), and 2) even the maximum dose of rhGM-CSF increased erythroid bursts to a lesser extent than was possible by the addition of rhIL-3. The former results implies that BPA is not the major activity of GM-CSF, and the latter result, although it is not conclusive, suggests that the GM-CSF-responsive BFU-E represent only a subset population of BFU-E responsive to IL-3. The two-stage culture is a useful assay method for screening BPA in biological materials with respect to accuracy, dose responsiveness, and reproducibility.
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PMID:Three quantitative assays for human erythroid burst-promoting activity of recombinant growth factors and of omentum-conditioned medium. 240 58

NFS-60 cells were previously obtained from leukemia cells that were infected with the Cas-Br-M murine leukemia virus in vivo. We examined the proliferation and differentiation capacity of NFS-60 cells in the presence of native and recombinant (r) interleukin 3 (IL-3), recombinant granulocyte colony-stimulating factor (rG-CSF), recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), and r-erythropoietin (Ep) using methylcellulose culture methods. This cell line was able to form colonies in response to each hemopoietic factor, but colony formation was rarely seen in their absence. Some populations of NFS-60 cells could differentiate into neutrophils and macrophages in the presence of IL-3 and GM-CSF. Moreover, in the presence of Ep, this cell line formed well-hemoglobinized colonies as well as nonerythroid colonies. In the presence of G-CSF, NFS-60 cells remained in the promyelocytic state. Electron microscopic studies confirmed these morphologies. A single-cell transfer experiment demonstrated that neutrophils, macrophages, and erythroblasts were derived from a single cell. It is concluded that the NFS-60 cell line is a factor-dependent, bipotential hemopoietic cell line.
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PMID:Bipotential murine hemopoietic cell line (NFS-60) that is responsive to IL-3, GM-CSF, G-CSF, and erythropoietin. 245 92

The effect of a number of purified or recombinant hematopoietic growth factors, including recombinant erythropoietin (rEpo), thrombocytopoiesis stimulating factor (TSF), recombinant interleukin 1 alpha (rIL-1 alpha), recombinant granulocyte colony-stimulating factor (rG-CSF), macrophage colony-stimulating factor (CSF-1), recombinant interleukin 3 (rIL-3), and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on megakaryocyte (MK) colony formation by normal human marrow cells in a serum-depleted assay system was determined. Neither rEpo, TSF, CSF-1, rIL-1 alpha, nor rG-CSF alone augmented MK colony formation. Both rGM-CSF and rIL-3 at optimal doses increased MK colony formation eightfold and tenfold, respectively, above baseline values. Addition of increasing amounts of either rGM-CSF or rIL-3 led to progressively greater numbers of MK colonies formed until plateau levels were reached. Both rGM-CSF and rIL-3 also led to a dose-related increase in the number of cells per MK colony formed in culture. These molecules were equivalent stimulators of MK colony formation when their effects at optimal concentrations were compared. The effects of rGM-CSF and rIL-3 were additive at suboptimal concentrations of rIL-3 in that colony formation by a combination of the two growth factors approximated the sum of colony formation by each growth factor alone. These data suggest that rGM-CSF and rIL-3 alone and in combination are important regulators of in vitro megakaryocytopoiesis at the progenitor cell level.
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PMID:Effect of recombinant and purified hematopoietic growth factors on human megakaryocyte colony formation. 245 73

Myeloid and erythroid progenitor cells were enriched from human marrow by selecting CD34-positive (CD34 + ve) cells, labeled with the My10 (HPCA-1) antibody, using a fluorescence-activated cell sorter. Seventy-one percent of CD34 + ve cells were blasts and most of these were too primitive to be identified by standard morphological criteria. On average, 9.5% of CD34 + ve cells formed clones after 14 days of culture in semisolid medium supplemented with erythropoietin and medium conditioned by 5637 bladder carcinoma cells. Over 2.5% of CD34 + ve cells were day-14 myeloid colony-forming cells and 2.4% were erythroid colony (burst)-forming progenitors. The remaining progenitors formed myeloid and erythroid clusters. A subpopulation of day-14 myeloid colony-forming cells failed to respond to recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) after accessory cells were removed during enrichment, so it appears that this factor can induce myeloid growth indirectly as well as directly. Recombinant human GM-CSF also supported erythroid colony-formation in cultures of CD34 + ve cells, which suggests that this hemopoietin may act directly on erythroid progenitors.
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PMID:Enrichment of CD34 (My10)-positive myeloid and erythroid progenitors from human marrow and their growth in cultures supplemented with recombinant human granulocyte-macrophage colony-stimulating factor. 245 55


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