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dc.contributor.authorDevi, Sapna
dc.contributor.authorWang, Yilin
dc.contributor.authorChew, Weng Keong
dc.contributor.authorLima, Ronald
dc.contributor.authorA-Gonzalez, Noelia 
dc.contributor.authorMattar, Citra N Z
dc.contributor.authorChong, Shu Zhen
dc.contributor.authorSchlitzer, Andreas
dc.contributor.authorBakocevic, Nadja
dc.contributor.authorChew, Samantha
dc.contributor.authorKeeble, Jo L
dc.contributor.authorGoh, Chi Ching
dc.contributor.authorLi, Jackson L Y
dc.contributor.authorEvrard, Maximilien
dc.contributor.authorMalleret, Benoit
dc.contributor.authorLarbi, Anis
dc.contributor.authorRenia, Laurent
dc.contributor.authorHaniffa, Muzlifah
dc.contributor.authorTan, Suet Mien
dc.contributor.authorChan, Jerry K Y
dc.contributor.authorBalabanian, Karl
dc.contributor.authorNagasawa, Takashi
dc.contributor.authorBachelerie, Françoise
dc.contributor.authorHidalgo, Andrés 
dc.contributor.authorGinhoux, Florent
dc.contributor.authorKubes, Paul
dc.contributor.authorNg, Lai Guan
dc.identifier.citationJ Exp Med. 2013, 210(11): 2321-36es_ES
dc.description.abstractBlood 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.es_ES
dc.description.sponsorshipThis research was funded by SIgN, A*STAR, Singapore. C.N.Z. Mattar and J.K.Y. Chan received salary support from the National Medical Research Council of Singapore (NMRC/TA/003/2012 and NMRC/CSA/012/2009, respectively).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBone Marrow es_ES
dc.subject.meshCell Movement es_ES
dc.subject.meshGranulocyte Colony-Stimulating Factor es_ES
dc.subject.meshGreen Fluorescent Proteins es_ES
dc.subject.meshHeterocyclic Compounds es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLeukocyte Count es_ES
dc.subject.meshLung es_ES
dc.subject.meshMacaca fascicularis es_ES
dc.subject.meshMice es_ES
dc.subject.meshMicroscopy, Fluorescence, Multiphoton es_ES
dc.subject.meshMuramidase es_ES
dc.subject.meshMuscle, Skeletales_ES
dc.subject.meshMutation es_ES
dc.subject.meshNeutrophils es_ES
dc.subject.meshPulmonary Circulation es_ES
dc.subject.meshReceptors, CXCR4 es_ES
dc.subject.meshReceptors, Interleukin-8B es_ES
dc.titleNeutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrowes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderNational Medical Research Council of Sicngaporees_ES
dc.identifier.journalThe Journal of experimental medicinees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen de la Inflamación Cardiovascular y la Respuesta Inmunees_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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