Granulocyte kinetics in neutrophilia induced by recombinant human granulocyte colony-stimulating factor in mice

To investigate the mechanisms of neutrophilic expansion induced by granulocyte colony-stimulating factor (G-CSF), granulocyte kinetics was studied by means of an autoradiographic method in G-CSF treated mice. Daily intraperitoneal injections of recombinant human G-CSF (rhG-CSF; 2.5 micrograms/day for 5 days) markedly increased the white blood cell count, especially granulocytes in circulating blood. Whole body bone marrow cellularity, quantitated using the radiodilution principle described by Donohue and Finch, increased from 30.0 x 10(7) cells/body (15.2 x 10(9) cells/kg) to 83.5 x 10(7) (41.8 x 10(9)) after the administration of rhG-CSF for 3 days. Generation time of myeloblasts, mitotic pool transit time, and post-mitotic pool transit time, assessed by autoradiography with 3H-thymidine, were significantly shortened in rhG-CSF treated mice compared with the control mice. Daily neutrophil production rates, calculated from these parameters, were 15. 61 x 10(7) cells/day in rhG-CSF mice and 1.93 x 10(7) in the controls. rhG-CSF had no significant effect on the survival time of granulocytes in the circulation, assessed by T1/2 of 3H-thymidine labeled granulocytes. Thus, neutrophilia induced by rhG-CSF is partly due to shortening of the generation time, mitotic pool transit time and post-mitotic pool transit time of myeloid cells.