Imperial College London
Alternate

ProfessorSaraRankin

Faculty of Medicine, National Heart & Lung Institute

Professor of Leukocyte and Stem Cell Biology
 
 
 
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Contact

 

+44 (0)20 7594 3172s.rankin

 
 
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Assistant

 

Ms Georgina Moss +44 (0)20 7594 2151

 
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Location

 

Office no. 351Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Redpath:2017:10.1182/bloodadvances.2017006064,
author = {Redpath, AN and Francois, M and Wong, S-P and Bonnet, D and Rankin, SM},
doi = {10.1182/bloodadvances.2017006064},
journal = {BLOOD ADVANCES},
pages = {1934--1943},
title = {Two distinct CXCR4 antagonists mobilize progenitor cells in mice by different mechanisms},
url = {http://dx.doi.org/10.1182/bloodadvances.2017006064},
volume = {1},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pharmacological mobilization of hematopoietic progenitor cells (HPCs) is used clinically to harvest HPCs for bone marrow transplants. It is now widely accepted that the CXCR4:CXCL12 chemokine axis plays a critical role in the retention of HPCs in the bone marrow, and CXCR4 antagonists have been developed for their mobilization. The first of this class of drugs to be US Food and Drug Administration-approved was the bicyclam AMD3100. In addition to mobilizing HPCs and leukocytes in naïve mice, AMD3100 has been shown to mobilize mesenchymal progenitor cells (MPCs) in vascular endothelial growth factor (VEGF-A) pretreated mice. AMD3100 binds to the transmembrane region of CXCR4 and is thought to mobilize HPCs by reversing the gradient of CXCL12 across the bone marrow endothelium. Consistent with this hypothesis, our data show that selective neutralization of CXCL12, with chalcone 4-phosphate (C4P), inhibited AMD3100-stimulated mobilization of HPCs and leukocytes in naïve mice and MPCs in VEGF-A pretreated mice. In contrast it is shown here that the CXCR4 antagonist KRH3955 that binds to the extracellular loop of CXCR4 does not reverse the CXCL12 chemokine gradient. However, this drug efficiently mobilizes HPCs, a response that is not inhibited by C4P. In contrast, KRH3955 does not mobilize MPCs in VEGF-A pretreated mice. These data suggest that CXCR4 antagonists that bind to distinct regions of the receptor mobilize progenitor cells by distinct molecular mechanisms.
AU  - Redpath,AN
AU  - Francois,M
AU  - Wong,S-P
AU  - Bonnet,D
AU  - Rankin,SM
DO  - 10.1182/bloodadvances.2017006064
EP  - 1943
PY  - 2017///
SN  - 2473-9529
SP  - 1934
TI  - Two distinct CXCR4 antagonists mobilize progenitor cells in mice by different mechanisms
T2  - BLOOD ADVANCES
UR  - http://dx.doi.org/10.1182/bloodadvances.2017006064
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000412736200008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/55267
VL  - 1
ER  -
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