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

We have compared the efficacy of a single injection of SD/01, a newly engin eered, pegylated form of recombinant human granulocyte colony stimulating f actor (rhG-CSF), with a single injection of glycosylated rhG-CSF (Filgrasti m). SD/01 was administered to regular and recombinant inbred strains of mic e (AKR, C557L/J, DBA/2, C57BL/6, AKXL) known to have widely distinct marrow -cell pool sizes and proliferation kinetics. A single injection of G-CSF wa s 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 qualitative ly similar mobilization responses, large interstrain differences remained. C57L and C57BL/6 mice mobilized relatively poorly, whereas AKR and DBA/2, m ice showed threefold to tenfold superior responses, In order to explain the se different phenotypes, we studied the effects of SD/01 in nine AKXL recom binant inbred strains, derived from well-responding AKR and poorly respondi ng C57L parental strains. The best predictor for SD/01 responsiveness in th ese strains was marrow cellularity prior to mobilization. Comparison of the AKXL strain distribution pattern for marrow cellularity with loci previous ly mapped in these strains showed complete concordance with Ant, a serine p rotease inhibitor mapping to chromosome 12.