Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 1997 Jul 15;90(2):605-11.

Inhibition of immature erythroid progenitor cell proliferation by macrophage inflammatory protein-1alpha by interacting mainly with a C-C chemokine receptor, CCR1.

Author information

  • 1Department of Pharmacology, Cancer Research Institute, School of Medicine, Kanazawa University, Japan.

Abstract

Several lines of evidence indicate that macrophage inflammatory protein-1alpha (MIP-1alpha) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1alpha, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1alpha on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1alpha inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1alpha on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1alpha-mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

PMID:
9226160
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk