G-CSF Down-regulation of CXCR4 Expression Identified As a Mechanism for Mobilization of Myeloid Cells

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2006 Mar 16

PMID 16537807

Citations 93

Authors

Hyun Kyung Kim

Maria De La Luz Sierra

Cassin Kimmel Williams

A Virginia Gulino

Giovanna Tosato

Affiliations

Soon will be listed here.

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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