Inductive Potential of Recombinant Human Granulocyte Colony-Stimulating Factor to Mature Neutrophils from X-Irradiated Human Peripheral Blood Hematopoietic Progenitor Cells

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  • Katsumori Takeo
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences
  • Yoshino Hironori
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences
  • Hayashi Masako
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences
  • Takahashi Kenji
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences
  • Kashiwakura Ikuo
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences

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Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used for treatment of neutropenia. Filgrastim, Nartograstim, and Lenograstim are clinically available in Japan. However, the differences in potential benefit for radiation-induced disorder between these types of rhG-CSFs remain unknown. Therefore, the effects of three different types of rhG-CSFs on granulocyte progenitor cells and expansion of neutrophils from nonirradiated or 2 Gy X-irradiated human CD34+ hematopoietic progenitor cells were examined. For analysis of granulocyte colony-forming units (CFU-G) and a surviving fraction of CFU-G, nonirradiated or X-irradiated CD34+ cells were cultured in methylcellulose containing rhG-CSF. These cells were cultured in serum-free medium supplemented with rhG-CSF, and the expansion and characteristics of neutrophils were analyzed. All three types of rhG-CSFs increased the number of CFU-G in a dose-dependent manner; however, Lenograstim is superior to others because of CFU-G-derived colony formation at relatively low doses. The surviving fraction of CFU-G was independent of the types of rhG-CSFs. Expansion of neutrophils by rhG-CSF was largely attenuated by X-irradiation, though no significant difference in neutrophil number was observed between the three types of rhG-CSFs under both nonirradiation and X-irradiation conditions. In terms of functional characteristics of neutrophils, Lenograstim-induced neutrophils produced high levels of reactive oxygen species compared to Filgrastim, when rhG-CSF was applied to nonirradiated CD34+ cells. In conclusion, different types of rhG-CSFs lead to different effects when rhG-CSF is applied to nonirradiated CD34+ cells, though Filgrastim, Nartograstim, and Lenograstim show equal effects on X-irradiated CD34+ cells.

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