Inhibition of Immature Erythroid Progenitor Cell Proliferation by Macrophage Inflammatory Protein-1a by Interacting Mainly With a C-C Chemokine Receptor, CCR1

Several lines of evidence indicate that macrophage inflamerythroid (BFU-E), but not by colony forming unit-erythroid matory protein-1a (MIP-1a) modulates the proliferation of (CFU-E), in a methylcellulose culture of purified human hematopoietic progenitor cells, depending on their maturaCD34 bone marrow cells. Although reverse-transcription tional stages. To clarify the mechanisms for the modulation polymerase chain reaction (RT-PCR) showed the presence of hematopoiesis by this chemokine, we examined the exof CCR1, CCR4, and CCR5 transcripts in CD34 cells in BM, pression of a receptor for MIP-1a, CCR1, on bone marrow anti-CCR1 antibodies significantly abrogated the inhibitory cells of normal individuals using a specific antibody and exeffects of MIP-1a on BFU-E formation both in a methylcelluplored the effects of MIP-1a on in vitro erythropoiesis driven lose culture and in a single cell proliferation assay of purified by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was CD34 cells. Although the contribution of CCR4 or CCR5 canexpressed on glycophorin A-positive erythroblasts in addinot be completely excluded, these results suggest that MIPtion to lymphocytes and granulocytes. CCR1 cells, isolated 1a–mediated suppression of the proliferation of immature, from bone marrow mononuclear cells (BMMNCs) using a but not mature erythroid progenitor cells, is largely medicell sorter, comprised virtually all erythroid progenitor cells ated by CCR1 expressed on these progenitor cells. in the BMMNCs. Moreover, MIP-1a inhibited, in a dose-deq 1997 by The American Society of Hematology. pendent manner, colony formation by burst-forming unit-