Ehancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells

H. E. Broxmeyer, B. Sherry, L. Lu, S. Cooper, K. O. Oh, P. Tekamp-Olson, B. S. Kwon, A. Cerami

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1110-1116
Number of pages7
JournalBlood
Volume76
Issue number6
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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