Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF.
- 15 May 2000
- journal article
- Vol. 95 (10) , 3025-31
Abstract
The mechanisms that regulate hematopoietic progenitor cell (HPC) mobilization from the bone marrow to blood have not yet been defined. HPC mobilization by granulocyte colony-stimulating factor (G-CSF), cyclophosphamide (CY), or interleukin-8 but not flt-3 ligand is markedly impaired in G-CSF receptor-deficient (G-CSFR-deficient) mice. G-CSFR is expressed on mature hematopoietic 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 agents. To define the cell type(s) responsible for G-CSF-dependent mobilization, a series of chimeric mice were generated using bone marrow transplantation. Mobilization studies in these chimeras demonstrated that expression of the G-CSFR on transplantable hematopoietic cells but not stromal cells is required 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 colony-forming cells, CD34(+) lineage(-) and Sca(+) lineage(-) cells, and long-term culture initiating cells. Collectively, these data provide the first definitive 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.This publication has 0 references indexed in Scilit: