Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro.
The CXCR4 antagonist, AMD3100, stimulates a rapid increase in circulating numbers of haematopoeitic progenitor cells (HPCs) in both mice and human healthy volunteers. An in situ perfusion system of the mouse femoral bone marrow was used to provide the first direct evidence that AMD3100 mobilises HPCs from the bone marrow. Structural analogues of AMD3100 demonstrated that the ability of these compounds to mobilise HPCs in vivo correlated with their capacity to antagonise CXCR4 in vitro. This model system was also used to demonstrate additive effects of AMD3100 administered acutely, with granulocyte colony-stimulating factor administered chronically, with respect to HPC mobilisation.
Martin
Coralie
C
Leukocyte Biology Section, NHLI Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, South Kensington, UK.
Bridger
Gary J
GJ
Rankin
Sara M
SM
D000818:Animals; D001596:Benzylamines; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D000080027:Cyclams; D003864:Depression, Chemical; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000819:agonists / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor