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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/40895
Title: G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling
Authors: Besnik Bajrami
Haiyan Zhu
Hyun Jeong Kwak
Subhanjan Mondal
Qingming Hou
Guangfeng Geng
Kutay Karatepe
Yu C. Zhang
César Nombela-Arrieta
Shin Young Park
Fabien Loison
Jiro Sakai
Yuanfu Xu
Leslie E. Silberstein
Hongbo R. Luo
Harvard Medical School
Children's Hospital Boston
Dana-Farber/Harvard Cancer Center
Institute of Hematology and Blood Disease Hospital
UniversitatsSpital Zurich
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 1-Jan-2016
Citation: Journal of Experimental Medicine. Vol.213, No.10 (2016), 1999-2018
Abstract: © 2016 Bajrami et al. Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85016266410&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/40895
ISSN: 15409538
00221007
Appears in Collections:Scopus 2016-2017

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