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Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/...

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Autores principales: Zhang, Wen, Wang, Yao, Li, Chuanwei, Xu, Yu, Wang, Xia, Wu, Di, Gao, Zhan, Qian, Hang, You, Zaichun, Zhang, Zhiren, He, Binfeng, Wang, Guansong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671298/
https://www.ncbi.nlm.nih.gov/pubmed/34925338
http://dx.doi.org/10.3389/fimmu.2021.768435
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author Zhang, Wen
Wang, Yao
Li, Chuanwei
Xu, Yu
Wang, Xia
Wu, Di
Gao, Zhan
Qian, Hang
You, Zaichun
Zhang, Zhiren
He, Binfeng
Wang, Guansong
author_facet Zhang, Wen
Wang, Yao
Li, Chuanwei
Xu, Yu
Wang, Xia
Wu, Di
Gao, Zhan
Qian, Hang
You, Zaichun
Zhang, Zhiren
He, Binfeng
Wang, Guansong
author_sort Zhang, Wen
collection PubMed
description Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.
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spelling pubmed-86712982021-12-16 Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury Zhang, Wen Wang, Yao Li, Chuanwei Xu, Yu Wang, Xia Wu, Di Gao, Zhan Qian, Hang You, Zaichun Zhang, Zhiren He, Binfeng Wang, Guansong Front Immunol Immunology Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS. Frontiers Media S.A. 2021-12-01 /pmc/articles/PMC8671298/ /pubmed/34925338 http://dx.doi.org/10.3389/fimmu.2021.768435 Text en Copyright © 2021 Zhang, Wang, Li, Xu, Wang, Wu, Gao, Qian, You, Zhang, He and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Wen
Wang, Yao
Li, Chuanwei
Xu, Yu
Wang, Xia
Wu, Di
Gao, Zhan
Qian, Hang
You, Zaichun
Zhang, Zhiren
He, Binfeng
Wang, Guansong
Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_full Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_fullStr Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_full_unstemmed Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_short Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_sort extracellular cirp-impaired rab26 restrains epor-mediated macrophage polarization in acute lung injury
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671298/
https://www.ncbi.nlm.nih.gov/pubmed/34925338
http://dx.doi.org/10.3389/fimmu.2021.768435
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