Dominant myelopoietic effector functions mediated by chemokine receptor CCR1

Hal E. Broxmeyer, Scott Cooper, Giao Hangoc, Ji Liang Gao, Philip M. Murphy

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Macrophage inflammatory protein (MIP)-1α, a CC chemokine, enhances proliferation of mature subsets of myeloid progenitor cells (MPCs), suppresses proliferation of immature MPCs, and mobilizes mature and immature MPCs to the blood. MIP-1α binds at least three chemokine receptors. To determine if CCR1 was dominantly mediating the above activities of MIP-1α CCR1-deficient (-/-) mice, produced by targeted gene disruption, were used. MIP-1α enhanced colony formation of marrow granulocyte/macrophage colony- forming units (CFU-GM), responsive to stimulation by granulocyte/macrophage colony-stimulating factor (GM-CSF), and CFU-M, responsive to stimulation by M-CSF, from littermate control CCR1(+/+) but not CCR1(-/-) mice. Moreover, MIP-1α did not mobilize MPCs to the blood or synergize with G-CSF in this effect in CCR1(-/-) mice. However, CCR1(-/-) mice were increased in sensitivity to MPC mobilizing effects of G-CSF. Multi-growth factor- stimulated MPCs in CCR1(-/-) and CCR1(+/+) marrow were equally sensitive to inhibition by MIP-1α. These results implicate CCR1 as a dominant receptor for MIP-1α enhancement of proliferation of lineage-committed MPCs and for mobilization of MPCs to the blood. CCR1 is not a dominant receptor for MIP- lα suppression of MPC proliferation, but it does negatively impact G-CSF- induced MPC mobilization.

Original languageEnglish (US)
Pages (from-to)1987-1992
Number of pages6
JournalJournal of Experimental Medicine
Volume189
Issue number12
DOIs
StatePublished - Jun 21 1999

Keywords

  • CC chemokine receptor 1
  • Macrophage inflammatory protein lα
  • Mobilization
  • Progenitor cells
  • Proliferation

ASJC Scopus subject areas

  • Immunology

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