CXCR4 and mobilization of hematopoietic precursors.
The binding of the chemokine [C-X-C motif] ligand 12 (CXCL12 or stromal cell-derived factor 1alpha [SDF-1alpha]) constitutively produced by bone marrow stromal cells and osteoblasts, to the CXC receptor (CXCR) 4, a transmembrane chemokine receptor expressed on hematopoietic stem and progenitor cells (HSPCs), has emerged as a key signal for HSPC trafficking to and from the bone marrow. Disruption of CXCL12/CXCR4 signaling causes leukocytosis, with the release of HSPCs, neutrophils, and lymphocytes into the peripheral blood. Although mobilized peripheral blood has become the preferred source of stem cells for both autologous and allogeneic transplantation, the optimum strategy for obtaining mobilized products from donors is the subject of ongoing study. Granulocyte colony-stimulating factor (G-CSF) and plerixafor (AMD3100) are two agents used clinically to induce HSPC mobilization by disruption of the CXCL12/CXCR4 interaction. This chapter describes current procedures used to phenotypically and functionally characterize murine and human HSPCs mobilized by G-CSF or plerixafor.
Rettig
Michael P
MP
Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA.
Ramirez
Pablo
P
Nervi
Bruno
B
DiPersio
John F
JF
D000818:Animals; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism*
D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor