G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells

• Published in: Blood 2006-08, Vol.108 (3), p.812-820
• Main Authors: Kim, Hyun Kyung, De La Luz Sierra, Maria, Williams, Cassin Kimmel, Gulino, A. Virginia, Tosato, Giovanna
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells; Chemokine CXCL12; Chemokines, CXC - physiology; Chemokines, Cytokines, and Interleukins; Down-Regulation - drug effects; Down-Regulation - genetics; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Mobilization - methods; Immunobiology; Mice; Mice, Inbred C57BL; Myeloid Cells - drug effects; Myeloid Cells - metabolism; Myeloid cells: ontogeny, maturation, markers, receptors; Polynuclears; Receptors, CXCR4 - drug effects; Receptors, CXCR4 - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-10-4162

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.