S-Space College of Medicine/School of Medicine (의과대학/대학원) Laboratory Medicine (검사의학전공) Journal Papers (저널논문_검사의학전공)
G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells
- Kim, Hyun Kyung; De La Luz Sierra, Maria; Williams, Cassin Kimmel; Gulino, A Virginia; Tosato, Giovanna
- Issue Date
- American Society of Hematology
- Blood. 2006;108:812-820
- Bone Marrow Cells; Chemokine CXCL12; Chemokines, CXC/physiology; Down-Regulation/*drug effects/genetics; Granulocyte Colony-Stimulating Factor/administration &; dosage/*pharmacology; Hematopoietic Stem Cell Mobilization/*methods; Mice, Inbred C57BL; Myeloid Cells/drug effects/metabolism; Receptors, CXCR4/*drug effects/genetics
- 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.
- 0006-4971 (Print)
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