To evaluate the mechanism of neutrophilia by granulocyte colony-stimulating factor (G-CSF), kinetic studies with tritiated thymidine ([3H]TdR) were performed in mice. G-CSF increased the number of circulating metamyelocytes and band and segmented neutrophils after the daily injection of G-CSF. The production of neutrophils has been estimated from the number of postmitotic neutrophils and the marrow transit time of [3H]TdR-labeled neutrophils on day 4 of daily G-CSF injection. The number of postmitotic neutrophils was determined by the radioiron dilution method and by the neutrophil and erythroid ratio in bone marrow smears. The mean values for marrow postmitotic neutrophils in the G-CSF-treated group and the controls were 71 +/- 50 x 10(7) cells and 9.3 +/- 4.2 x 10(7) cells (mean +/- SD), respectively. The mean marrow transit time derived from myelocyte metamyelocyte transition time and the emergence of [3H]TdR-labeled cells into the peripheral blood was 45 h in the G-CSF group and 116 h in the controls. Thus, the daily neutrophil turnover was estimated to be 38 x 10(7) cells/day and 1.9 x 10(7) cells/day, respectively. Our results suggest that C-CSF markedly increases the neutrophil precursors and shortens the transit time in the mitotic and postmitotic pool.
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