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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells
Hyun Kyung Kim1, Maria De La Luz Sierra, Cassin Kimmel Williams
1Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Insights
Granulocyte-colony stimulating factor (G-CSF) reduces CXCR4 receptor expression on myeloid cells in bone marrow. This down-regulation promotes the mobilization of these cells into peripheral blood.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- CXCR4 receptor and its ligand SDF-1 are crucial for retaining myeloid cells in bone marrow.
- Disruption of the SDF-1/CXCR4 axis leads to myeloid cell mobilization into circulation.
Purpose of the Study:
- To investigate the effect of G-CSF on CXCR4 expression in myeloid lineage cells.
- To elucidate the mechanism by which G-CSF influences myeloid cell mobilization from bone marrow.
Main Methods:
- Treatment of murine and human myeloid cells with G-CSF.
- Assessment of cell-surface CXCR4 expression using flow cytometry.
- Evaluation of cell attachment and migration in response to SDF-1.
- Analysis of CXCR4 expression in myeloid cells from G-CSF-treated mice.
Main Results:
- G-CSF treatment caused a time-dependent reduction in CXCR4 expression on bone marrow-derived myeloid cells.
- G-CSF-treated myeloid cells showed diminished responsiveness to SDF-1 in functional assays.
- Non-myeloid lineage cells did not exhibit changes in CXCR4 expression upon G-CSF exposure.
- G-CSF directly down-regulates CXCR4 on myeloid cells expressing G-CSF receptors.
Conclusions:
- G-CSF directly reduces CXCR4 expression in bone marrow myeloid cells.
- Down-regulation of CXCR4 by G-CSF attenuates myeloid cell responsiveness to SDF-1.
- G-CSF promotes myeloid cell mobilization from bone marrow by decreasing CXCR4 expression.
Abstract:
CXCR4 receptor expression is required for the retention of granulocyte precursors and mature neutrophils within the bone marrow, and disruption of the SDF-1/CXCR4 axis in the bone marrow results in the mobilization of myeloid lineage cells to the peripheral circulation. We report that G-CSF down-regulates CXCR4 expression in bone marrow-derived murine and human myeloid lineage cells. When exposed to G-CSF, murine Gr1(+) bone marrow myeloid cells display a time-dependent reduction of cell-surface CXCR4 and respond poorly to SDF-1 in attachment and migration assays. Bone marrow-derived cells of nonmyeloid lineage display no change in surface CXCR4 expression upon exposure to G-CSF. Compared with controls, mice treated with G-CSF for mobilization of hematopoietic progenitor cells display reduced levels of CXCR4 selectively in bone marrow Gr1(+) myeloid cells. Since bone marrow myeloid cells express G-CSF receptors and G-CSF rapidly reduces CXCR4 expression in purified Gr1(+) cells populations, these results provide evidence that G-CSF acts directly on myeloid lineage cells to reduce CXCR4 expression. By down-regulating CXCR4 expression in bone marrow myeloid cells and attenuating their responsiveness to SDF-1, G-CSF promotes their mobilization from the bone marrow to the peripheral blood.
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