Cargando…
G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling
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 acut...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030805/ https://www.ncbi.nlm.nih.gov/pubmed/27551153 http://dx.doi.org/10.1084/jem.20160393 |
_version_ | 1782454741669773312 |
---|---|
author | Bajrami, Besnik Zhu, Haiyan Kwak, Hyun-Jeong Mondal, Subhanjan Hou, Qingming Geng, Guangfeng Karatepe, Kutay Zhang, Yu C. Nombela-Arrieta, César Park, Shin-Young Loison, Fabien Sakai, Jiro Xu, Yuanfu Silberstein, Leslie E. Luo, Hongbo R. |
author_facet | Bajrami, Besnik Zhu, Haiyan Kwak, Hyun-Jeong Mondal, Subhanjan Hou, Qingming Geng, Guangfeng Karatepe, Kutay Zhang, Yu C. Nombela-Arrieta, César Park, Shin-Young Loison, Fabien Sakai, Jiro Xu, Yuanfu Silberstein, Leslie E. Luo, Hongbo R. |
author_sort | Bajrami, Besnik |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5030805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50308052017-03-19 G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling Bajrami, Besnik Zhu, Haiyan Kwak, Hyun-Jeong Mondal, Subhanjan Hou, Qingming Geng, Guangfeng Karatepe, Kutay Zhang, Yu C. Nombela-Arrieta, César Park, Shin-Young Loison, Fabien Sakai, Jiro Xu, Yuanfu Silberstein, Leslie E. Luo, Hongbo R. J Exp Med Research Articles 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. The Rockefeller University Press 2016-09-19 /pmc/articles/PMC5030805/ /pubmed/27551153 http://dx.doi.org/10.1084/jem.20160393 Text en © 2016 Bajrami 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 http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Bajrami, Besnik Zhu, Haiyan Kwak, Hyun-Jeong Mondal, Subhanjan Hou, Qingming Geng, Guangfeng Karatepe, Kutay Zhang, Yu C. Nombela-Arrieta, César Park, Shin-Young Loison, Fabien Sakai, Jiro Xu, Yuanfu Silberstein, Leslie E. Luo, Hongbo R. G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title | G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title_full | G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title_fullStr | G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title_full_unstemmed | G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title_short | G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling |
title_sort | g-csf maintains controlled neutrophil mobilization during acute inflammation by negatively regulating cxcr2 signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030805/ https://www.ncbi.nlm.nih.gov/pubmed/27551153 http://dx.doi.org/10.1084/jem.20160393 |
work_keys_str_mv | AT bajramibesnik gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT zhuhaiyan gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT kwakhyunjeong gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT mondalsubhanjan gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT houqingming gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT gengguangfeng gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT karatepekutay gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT zhangyuc gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT nombelaarrietacesar gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT parkshinyoung gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT loisonfabien gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT sakaijiro gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT xuyuanfu gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT silbersteinlesliee gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling AT luohongbor gcsfmaintainscontrolledneutrophilmobilizationduringacuteinflammationbynegativelyregulatingcxcr2signaling |