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Title: Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
Authors: Devi, Sapna
Wang, Yilin
Chew, Weng Keong
Lima, Ronald
A-González, Noelia
Mattar, Citra N. Z.
Chong, Shu Zhen
Schlitzer, Andreas
Bakocevic, Nadja
Chew, Samantha
Keeble, Jo L.
Goh, Chi Ching
Li, Jackson L. Y.
Evrard, Maximilien
Malleret, Benoit
Larbi, Anis
Renia, Laurent
Haniffa, Muzlifah
Tan, Suet Mien
Chan, Jerry Kok Yen
Balabanian, Karl
Nagasawa, Takashi
Bachelerie, Françoise
Hidalgo, Andrés
Ginhoux, Florent
Kubes, Paul
Ng, Lai Guan
Keywords: DRNTU::Science::Medicine
Issue Date: 2013
Source: Devi, S., Wang, Y., Chew, W. K., Lima, R., A-González, N., Mattar, C. N. Z., & et al. (2013). Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. Journal of experimental medicine, 210(11), 2321-2336.
Series/Report no.: Journal of experimental medicine
Abstract: Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.
ISSN: 0022-1007
DOI: 10.1084/jem.20130056
Schools: School of Biological Sciences 
Rights: © 2013 Devi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–oncommercial–Share Alike 3.0 Unported license, as described at
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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