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

Cited 136 time in Web of Science Cited 143 time in Scopus
Authors
Kim, Hyun Kyung; De La Luz Sierra, Maria; Williams, Cassin Kimmel; Gulino, A Virginia; Tosato, Giovanna
Issue Date
2006-08-01
Publisher
American Society of Hematology
Citation
Blood. 2006;108:812-820
Keywords
Bone Marrow CellsChemokine CXCL12Chemokines, CXC/physiologyDown-Regulation/*drug effects/geneticsGranulocyte Colony-Stimulating Factor/administration &dosage/*pharmacologyHematopoietic Stem Cell Mobilization/*methodsMice, Inbred C57BLMyeloid Cells/drug effects/metabolismReceptors, CXCR4/*drug effects/genetics
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.
ISSN
0006-4971 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16537807

http://hdl.handle.net/10371/11870
DOI
https://doi.org/10.1182/blood-2005-10-4162
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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