Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony-stimulating factor in mouse strains with distinct marrow-cell pool sizes

We have compared the efficacy of a single injection of SD/01, a newly engineered, pegylated form of recombinant human granulocyte colony stimulating factor (rhG-CSF), with a single injection of glycosylated rhG-CSF (Filgrastim). SD/01 was administered to regular and recombinant inbred strains of mice (AKR, C57L/J, DBA/2, C57BL/6, AKXL) known to have widely distinct marrow-cell pool sizes and proliferation kinetics. A single injection of G-CSF was unable to mobilize granulocyte–macrophage colony-forming units (CFU-GM). In sharp contrast, a single dose of SD/01 resulted in massive mobilization of progenitors and stem cells. Although all mice strains showed qualitatively similar mobilization responses, large interstrain differences remained. C57L and C57BL/6 mice mobilized relatively poorly, whereas AKR and DBA/2 mice showed threefold to tenfold superior responses. In order to explain these different phenotypes, we studied the effects of SD/01 in nine AKXL recombinant inbred strains, derived from well-responding AKR and poorly responding C57L parental strains. The best predictor for SD/01 responsiveness in these strains was marrow cellularity prior to mobilization. Comparison of the AKXL strain distribution pattern for marrow cellularity with loci previously mapped in these strains showed complete concordance with Aat, a serine protease inhibitor mapping to chromosome 12.