ENHANCING AND SUPPRESSING EFFECTS OF RECOMBINANT MURINE MACROPHAGE INFLAMMATORY PROTEINS ON COLONY FORMATION INVITRO BY BONE-MARROW MYELOID PROGENITOR CELLS

Google Scholar
  • 15 September 1990
    • journal article
    • research article
    • Vol. 76  (6) , 1110-1116
Abstract
Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1.alpha., 1.beta., and 2 were assessed for effects on murine (mu) and human (hu) marrow colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies. Recombinant MIP-1.alpha., -1.beta., 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-1.alpha., but not rMIP-1.beta. 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 rhuIL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1.alpha. 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-1.alpha., -1.beta., and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1.alpha. may have direct suppressing activity for more immature progenitors.

This publication has 12 references indexed in Scilit: