Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF

The mechanisms that regulate hematopoietic progenitor cell (HPC) mobilizati on from the bone marrow to blood have not yet been defined, HPC mobilizatio n by granulocyte colony-stimulating factor (G-CSF), cyclophosphamide (CY), or interleukin-8 but not flt-3 ligand is markedly impaired in G-CSF recepto r-deficient (G-CSFR-deficient) mice. G-CSFR is expressed on mature hematopo ietic cells, HPCs, and stromal cells, which suggests that G-CSFR signals in one or more of these cell types was required for mobilization by these age nts. To define the cell type(s) responsible for G-CSF-dependent mobilizatio n, a series of chimeric mice were generated using bone marrow transplantati on. Mobilization studies in these chimeras demonstrated that expression of the G-CSFR on transplantable hematopoietic cells but not stromal cells is r equired for CY- or G-CSF-induced mobilization. Moreover, in irradiated mice reconstituted with both wild type and G-CSFR-deficient bone marrow cells, treatment with CY or G-CSF resulted in the equal mobilization of both types of HPCs. This result held true; for a broad spectrum of HPCs including col ony-forming cells, CD34(+) lineage(-) and Sca(+) lineage- cells, and long-t erm culture initiating cells. Collectively, these data provide the first de finitive evidence that expression of the G-CSFR on HPCs is not required for their mobilization by G-CSF and suggest a model in which G-CSFR-dependent signals act in trans to mobilize HPCs from the bone marrow, (C) 2000 by The American Society of Hematology.