Noncycling state of peripheral blood progenitor cells mobilized by granulocyte colony-stimulating factor and other cytokines

Abstract

Incubation with high doses of tritiated thymidine in vitro was used to determine the percent of progenitor cells in the S phase of the cell cycle. Peripheral blood (PB), bone marrow (BM), and spleen populations from mice injected with granulocyte colony-stimulating factor (G-CSF) at 5 μg/day for 5 days and BM cells from uninjected littermates were assayed. Although the percentage of progenitor cells in S phase in the marrow (47% ± 5%) and spleen (52% ± 9%) was increased significantly in G-CSF-treated mice, only a small proportion of PB progenitor cells (PBPC) were in S phase (7% ± 4%). In normal human subjects injected with G-CSF at 5 or 10 μg/kg/d, the proportions of PB myeloid (-1 ± 4%) and erythroid (0% ± 8%) progenitor cells in S phase were very low compared with the proportion of myeloid progenitor cells in S phase in normal BM (34% ± 10%). Similarly, the large majority of steady-state PBPC and PBPC mobilized by interleukin-3 in combination with either granulocyte-macrophage colony-stimulating factor or G-CSF were also found not to be in S phase. Experiments indicated that the low percentages of PBPC in S phase were not ascribable either to inhibitory elements in the blood or to reduced responsiveness to growth factors.