Macrophage inflammatory protein (MIP)-1β abrogates the capacity of MIP-1α to suppress myeloid progenitor cell growth

H. E. Broxmeyer, B. Sherry, S. Cooper, F. W. Ruscetti, D. E. Williams, P. Arosio, B. S. Kwon, A. Cerami

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70 Scopus citations

Abstract

The effects of recombinant murine macrophage inflammatory protein (MIP)-1β and MIP-2 on the suppressive activity of MIP-1α were tested using colony formation by human and murine bone marrow burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte erythroid macrophage, megakaryocyte (CFU-GEMM), and colony-forming unit-granulocyte macrophage (CFU-GM) progenitor cells. MIP-1β, but not MIP-2, when added with MIP-1α to cells, blocked the suppressive effects of MIP-1α on both human and murine BFU-E, CFU-GEMM, and CFU-GM colony formation. Similar results were observed regardless of the early acting cytokines used: human rGM-CSF plus human rIL-3, and two recently described potent cytokines, a genetically engineered human rGM-CSF/IL-3 fusion protein and MGF, a c-kit ligand. The more potent the stimuli, the greater the suppressive activity noted. Pulse treatment of hu bone marrow cells with MIP-1α at 4°C for 1 h was as effective in inhibiting colony formation as continuous exposure of cells to MIP-1α, and the pulsing effect with MIP-1α could not be overcome by subsequent exposure of cells to MIP-1β. Also, pulse exposure of cells to MIP-1β blocked the activity of subsequently added MIP-1α. For specificity, the action of a nonrelated myelosuppressive factor H-ferritin, was compared. MIP-1α and H-ferritin were shown to act on similar target populations of early BFU-E, CFU-GEMM, and CFU-GM. MIP-1β did not block the suppressive activity of H-ferritin. Also, hemin and an inactive recombinant human H-ferritin mutein counteracted the suppressive effects of the wildtype H-ferritin molecule, but did not block the suppressive effects of MIP-1α. These results show that MIP-1β's ability to block the action of MIP-1α is specific. In addition, the results suggest that MIP-1α and MIP-β can, through rapid action, modulate early myeloid progenitor cell proliferation.

Original languageEnglish (US)
Pages (from-to)2586-2594
Number of pages9
JournalJournal of Immunology
Volume147
Issue number8
StatePublished - Nov 8 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Broxmeyer, H. E., Sherry, B., Cooper, S., Ruscetti, F. W., Williams, D. E., Arosio, P., Kwon, B. S., & Cerami, A. (1991). Macrophage inflammatory protein (MIP)-1β abrogates the capacity of MIP-1α to suppress myeloid progenitor cell growth. Journal of Immunology, 147(8), 2586-2594.