Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1α, 1β, and 2 were assessed for effects on murine (mu) and human (hu) marrow colony-forming unitgranulocyte-macrophage (CFU-GM) and burst-forming uniterythroid (BFU-E) colonies. Recombinant MIP-1α, -1β, and -2 enhanced muCFU-GM colonies above that stimulated with 10 to 100 U natural mu macrophage-colony-stimulating factor (M-CSF) or rmuGM-CSF, with enhancement seen on huCFU-GM colony formation stimulated with suboptimal rhuM-CSF or rhuGM-CSF; effects were neutralized by respective MIP-specific antibodies. Macrophage inflammatory proteins had no effects on mu or huBFU-E colonies stimulated with erythropoietin (Epo). However, natural MIP-1 and rMIP-1α, but not rMIP-1β or -2. suppressed muCFU-GM stimulated with pokeweed mitogen spleen-conditioned medium (PWMSCM), huCFU-GM stimulated with optimal rhuGM-CSF plus rhu interleukin-3 (IL-3), muBFU-E and multipotential progenitors (CFU-GEMM) stimulated with Epo plus PWMSCM, and huBFU-E and CFU-GEMM stimulated with Epo plus rhulL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1α were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34+++HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75%. These results, along with our previous studies, suggest that MIP-1α, -1β, and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1α may have direct suppressing activity for more immature progenitors.
ASJC Scopus subject areas
- Cell Biology