2026-06-14T03:32:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/77692024-09-27T09:40:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Devi, Sapna
author
Wang, Yilin
author
Chew, Weng Keong
author
Lima, Ronald
author
Alonso-Gonzalez, Noelia
author
Mattar, Citra N Z
author
Chong, Shu Zhen
author
Schlitzer, Andreas
author
Bakocevic, Nadja
author
Chew, Samantha
author
Keeble, Jo L
author
Goh, Chi Ching
author
Li, Jackson L Y
author
Evrard, Maximilien
author
Malleret, Benoit
author
Larbi, Anis
author
Renia, Laurent
author
Haniffa, Muzlifah
author
Tan, Suet Mien
author
Chan, Jerry K Y
author
Balabanian, Karl
author
Nagasawa, Takashi
author
Bachelerie, Françoise
author
Hidalgo, Andres
author
Ginhoux, Florent
author
Kubes, Paul
author
Ng, Lai Guan
funder
National Medical Research Council (Singapur)
2019-06-13T06:56:05Z
2019-06-13T06:56:05Z
2013-10
J Exp Med. 2013, 210(11): 2321-36
10.1084/jem.20130056
1540-9538
0022-1007
The Journal of experimental medicine
24081949
http://hdl.handle.net/20.500.12105/7769
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.
eng
Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
journal article
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