title: Granulocyte colony-stimulating factor (G-CSF) induces synthesis of alkaline phosphatase in neutrophilic granulocytes of chronic myelogenous leukemia patients.
abstract: The monocyte, monocyte conditioned media (MoCM), giant cell tumor conditioned media (GCT) and a purified colony-stimulating factor (G-CSF) promote granulocyte-macrophage progenitors (CFU-GM) growth and differentiation along the neutrophil lineage and also induce alkaline phosphatase (NAP) synthesis in the neutrophilic cells of normal subjects and of patients with chronic phase chronic myelogenous leukemia (CML). However, it is not known if granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (CSF-1) or other cytokines can induce NAP synthesis from the neutrophilic cells of CML patients. The objective of this study were (a) to ascertain which of the three CFU-GM CSFs would induce NAP synthesis, and (b) to test if any of the other cytokines--interleukin-1 (IL-1), interleukin-2 (IL-2), alpha- and gamma-interferons (alpha-INF and r-INF), and phytohemagglutinin-stimulated T-cell conditioned media (TCM) would induce NAP synthesis. Light density cells obtained from the blood of patients with chronic phase CML were depleted of T cells and monocytes. These cells were cultured with various amounts of G-CSF, GM-CSF, CSF-1, IL-1, IL-2, alpha-INF, r-INF, MoCM, GCT and TCM in a suspension culture system over 6-7 days. Evaluation of the cultures indicated that G-CSF, MoCM and GCT, but not the other factors or cytokines, consistently induced NAP synthesis in a dose-dependent manner. Actinomycin-D and puromycin in separate cultures inhibited NAP synthesis without any significant reduction in cell counts. This indicated that NAP is not prepackaged in neutrophilic cells, and its synthesis occurs by a sequential transcription at the DNA level and translation at the ribosomal level. Our results suggest that the molecule which is responsible for promotion of CFU-GM growth and differentiation along the neutrophilic cell lineage is also responsible for derepression of NAP gene and initiation of NAP synthesis.
authors: Medical and Research Service, Veterans Administration Medical Center, Albany, New York 12208.
authors: G
authors: G
authors: Chikkappa
authors: G J
authors: GJ
authors: Wang
authors: D
authors: D
authors: Santella
authors: D
authors: D
authors: Pasquale
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000502:physiology*; D003470:Culture Media; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D003115:Colony-Stimulating Factors; D003470:Culture Media; D016179:Granulocyte Colony-Stimulating Factor; D003609:Dactinomycin; D000469:Alkaline Phosphatase