title: Granulocyte colony-stimulating factor promotes functional maturation of O-2 generating system during differentiation of HL-60 cells to neutrophil-like cells.
abstract: The effects of granulocyte colony-stimulating factor (G-CSF) on development of O-2 generating system during differentiation of HL-60 cells to neutrophil-like cells have been studied. G-CSF enhanced O-2 generating ability of HL-60 cells whose differentiation had been initiated by dimethylsulfoxide (DMSO) or retinoic acid (RA). The O-2 generations by the differentiated HL-60 cells in response to opsonized zymosan (OZ), formyl-Met-Leu-Phe (fMLP), and IgG-coated zymosan were increased two- to fourfold as a result of incubation of the cells undergoing the differentiation with G-CSF. The potentiation by G-CSF occurred in a dose-dependent manner with the maximum effect at about 10 ng/ml G-CSF. The effect of G-CSF could not be fully explained by up-regulation of the receptor expression on the HL-60 cells, because the number of C3bi receptors was not altered by G-CSF, whereas the expression of fMLP receptor was enhanced by G-CSF. On the other hand, the O2 generation of the differentiated cells activated by phorbol 12-myristate 13-acetate was not affected by the G-CSF treatment, suggesting that the biochemical events in the cells after PKC activation might not be enhanced by G-CSF. Assuming that the signaling pathways linking OZ or fMLP receptor might be enhanced by G-CSF, alteration in the cellular sn-1, 2-diacylglycerols (DAG) level upon stimulation with OZ or fMLP was compared between the G-CSF-treated and nontreated cells. Whereas DAG level was not increased by the stimulation in the cells treated with DMSO alone, a significant increase in DAG level upon the stimulation was observed in the cells treated with G-CSF and DMSO. These results suggest that G-CSF would enhance the organization of a receptor-linked DAG generating system in the differentiating cells, leading the cells to generate more O2.
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, 158 Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide