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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)

Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate megakaryocytic maturation of normal progenitor cells, such as interleukin 3 and 6 and granulocyte-macrophage colony-stimulating factor. However, the cells were induced to differentiate into megakaryocytes by treatment with some protein kinase inhibitors. The inhibition of v-abl tyrosine kinase activity preceded induction of differentiation of the cells treated with tyrosine kinase inhibitors such as genistein, herbimycin A, and erbstatin. Treatment of C1 cells with a v-abl antisense oligomer inhibited their proliferation and induced acetylcholinesterase activity, a typical marker of megakaryocytic differentiation. These results suggest that inhibition of v-abl function is associated with induction of megakaryocytic differentiation of C1 cells. Among the compounds tested, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of cyclic nucleotide-dependent and Ca(2+)-phospholipid-dependent (protein kinase C) protein kinases, was the most potent inducer of differentiation of C1 cells. However, the differentiation-inducing effect of H-7 was unlikely to be mediated through inhibition of protein kinase C or cyclic nucleotide-dependent kinases, because other types of inhibitors of these kinases were not effective, and a protein kinase activator (phorbol ester) induced differentiation of C1 cells. Moreover, neither v-abl mRNA expression nor v-abl kinase activity in C1 cells was affected by treatment with H-7. These findings indicate that induction of megakaryocytic differentiation by H-7 is not related to inhibition of v-abl kinase, but rather to some novel function of H-7.
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PMID:Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus. 165 10

We have devised a simultaneous assay system for megakaryocyte colony-stimulating factor (Meg-CSF) and megakaryocyte potentiator (Meg-Pot) by modifying a quantitative measuring technique for acetylcholinesterase activity (Ach-E) of megakaryocytes by automatic colorimetry using microplates. We cultured murine bone marrow cells treated with diisopropyl fluorophosphate in a serum-free system with serum-free pokeweek mitogen-stimulated spleen cell conditioned medium (PWM-SCM) and an unknown factor, preparing two microplates with the identical culture system. In the first plate, the total number of Ach-E-positive cells induced solely by the factor tested was indicative of Meg-CSF activity and additive increases in this parameter on simultaneous addition of PWM-SCM and the factor tested were indicative of early Meg-Pot activity. Total Ach-E activity (total change at optical density of 414 nm) per well was measured in the second plate to calculate total change at optical density of 414 nm per megakaryocyte, an indicator of late Meg-Pot activity. With this system, recombinant human erythropoietin showed both Meg-CSF and early and late Meg-Pot activities in in vitro megakaryopoiesis. Recombinant murine granulocyte-macrophage colony-stimulating factor possessed weak Meg-CSF and early Meg-Pot activity, whereas recombinant human granulocyte colony-stimulating factor exhibited late Meg-Pot activity and thrombocytopenic serum exhibited early and late Meg-Pot activities. This assay system is useful in screening Meg-CSF or Meg-Pot activities in unknown factors.
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PMID:Simultaneous assay for megakaryocyte colony-stimulating factor and megakaryocyte potentiator and its application. 169 13

To investigate the effect of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on murine megakaryocytopoiesis in vitro, the factor was added to both serum-free colony assays and liquid marrow cultures. GM-CSF had a significant megakaryocytic colony-stimulating activity. After 2 hours of preincubation with and without 10 ng/mL rGM-CSF, the percentage of megakaryocyte colony-forming cell (CFU-MK) in DNA synthesis was determined by tritiated-thymidine suicide using colony growth. The reduction of CFU-MK colony numbers in marrow culture was 47.5% +/- 9.9%, 20.9% +/- 5.2% (control), respectively, indicating that the factor affected cell cycle at CFU-MK levels. When acetylcholinesterase (AchE) production was measured fluorometrically after 4 days of liquid culture, rGM-CSF elicited an increase in AchE activity in a dose-dependent fashion. To determine if the hematopoietin acts directly on megakaryocytic differentiation, 2 ng/mL rGM-CSF was added to serum-free cultures of 295 single megakaryocytes isolated from CFU-MK colonies. An increase in size was observed in 65% of cells initially 10 to 20 microns in diameter, 71% of cells 20 to 30 microns, and 40% of cells greater than 30 microns. Conversely, in absence of GM-CSF, 17%, 31%, and 10% of cells in each group increased in diameter. These data suggest that rGM-CSF promotes murine megakaryocytopoiesis in vitro and that the response to the factor is direct. To determine if the factor influences megakaryocytic/thrombocytic lineage in vivo, 1 and 5 micrograms of rGM-CSF were administered intraperitoneally every 12 hours for 6 consecutive days. Although a two- to three-fold increase in peripheral granulocytes was observed, neither megakaryocytic progenitor cells or platelets changed. Histologic analysis of bone marrow megakaryocytes showed no increase in size and number. The in vivo studies demonstrated no effect of GM-CSF on thrombocytopoiesis. The discrepancies between the in vitro and in vivo effects of GM-CSF require additional investigations.
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PMID:Effect of recombinant granulocyte-macrophage colony-stimulating factor on murine thrombocytopoiesis in vitro and in vivo. 218 Apr 95