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Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway

Persistent inflammation in the secondary spinal cord injury (SCI) is an important reason for the failure of nerve repair, which is partly due to the continuous activation of local M1-like macrophage/microglia. It is reported that extracellular trap (ET) has been a new way of cell death, which can be...

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Autores principales: Zhang, Chengyi, Guo, Dong, Qiao, Hao, Li, Jie, Li, Jiaxi, Yang, Yubing, Chang, Su'e, Li, Fengtao, Wang, Dong, Li, Haopeng, He, Xijing, Wang, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713475/
https://www.ncbi.nlm.nih.gov/pubmed/36466087
http://dx.doi.org/10.1155/2022/9197940
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author Zhang, Chengyi
Guo, Dong
Qiao, Hao
Li, Jie
Li, Jiaxi
Yang, Yubing
Chang, Su'e
Li, Fengtao
Wang, Dong
Li, Haopeng
He, Xijing
Wang, Fang
author_facet Zhang, Chengyi
Guo, Dong
Qiao, Hao
Li, Jie
Li, Jiaxi
Yang, Yubing
Chang, Su'e
Li, Fengtao
Wang, Dong
Li, Haopeng
He, Xijing
Wang, Fang
author_sort Zhang, Chengyi
collection PubMed
description Persistent inflammation in the secondary spinal cord injury (SCI) is an important reason for the failure of nerve repair, which is partly due to the continuous activation of local M1-like macrophage/microglia. It is reported that extracellular trap (ET) has been a new way of cell death, which can be released by macrophages and named macrophage extracellular trap (Met). Furthermore, it exists widely in the pathophysiological process of many diseases, but it has been rarely studied in the field of SCI. In this study, we constructed a spinal cord contusion model and assessed the function outcome of SCI rats. We used immunofluorescence, flow cytometry, and transmission electron microscope (TEM) to demonstrate the existence of Mets. Besides, some related experiments had also been employed to explore the relationship between Mets and M1 polarization of macrophage/microglia. We also performed Co-IP and Western blotting to reveal a new extracellular proinflammatory signal pathway. Finally, we made a linear regression analysis between the concentrations of specific markers of Mets in human serum and ASIA scores. Briefly, our results suggested that macrophages infiltrated in SCI area could induce macrophage/microglia to differentiate into M1-like cells by releasing Mets, which may be achieved partly through LL37-P2X37-NF-κB signal pathway. However, limiting Mets could effectively inhibit M1 polarization and promote function recovery. In addition, the concentrations of Met related proteins in human serum showed high correlation with ASIA scores and could be applied to reflect the severity of SCI. In conclusion, Mets may be a new target for SCI therapy and a promising index for SCI assessment.
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spelling pubmed-97134752022-12-02 Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway Zhang, Chengyi Guo, Dong Qiao, Hao Li, Jie Li, Jiaxi Yang, Yubing Chang, Su'e Li, Fengtao Wang, Dong Li, Haopeng He, Xijing Wang, Fang Oxid Med Cell Longev Research Article Persistent inflammation in the secondary spinal cord injury (SCI) is an important reason for the failure of nerve repair, which is partly due to the continuous activation of local M1-like macrophage/microglia. It is reported that extracellular trap (ET) has been a new way of cell death, which can be released by macrophages and named macrophage extracellular trap (Met). Furthermore, it exists widely in the pathophysiological process of many diseases, but it has been rarely studied in the field of SCI. In this study, we constructed a spinal cord contusion model and assessed the function outcome of SCI rats. We used immunofluorescence, flow cytometry, and transmission electron microscope (TEM) to demonstrate the existence of Mets. Besides, some related experiments had also been employed to explore the relationship between Mets and M1 polarization of macrophage/microglia. We also performed Co-IP and Western blotting to reveal a new extracellular proinflammatory signal pathway. Finally, we made a linear regression analysis between the concentrations of specific markers of Mets in human serum and ASIA scores. Briefly, our results suggested that macrophages infiltrated in SCI area could induce macrophage/microglia to differentiate into M1-like cells by releasing Mets, which may be achieved partly through LL37-P2X37-NF-κB signal pathway. However, limiting Mets could effectively inhibit M1 polarization and promote function recovery. In addition, the concentrations of Met related proteins in human serum showed high correlation with ASIA scores and could be applied to reflect the severity of SCI. In conclusion, Mets may be a new target for SCI therapy and a promising index for SCI assessment. Hindawi 2022-11-23 /pmc/articles/PMC9713475/ /pubmed/36466087 http://dx.doi.org/10.1155/2022/9197940 Text en Copyright © 2022 Chengyi Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Chengyi
Guo, Dong
Qiao, Hao
Li, Jie
Li, Jiaxi
Yang, Yubing
Chang, Su'e
Li, Fengtao
Wang, Dong
Li, Haopeng
He, Xijing
Wang, Fang
Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title_full Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title_fullStr Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title_full_unstemmed Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title_short Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway
title_sort macrophage extracellular traps exacerbate secondary spinal cord injury by modulating macrophage/microglia polarization via ll37/p2x7r/nf-κb signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713475/
https://www.ncbi.nlm.nih.gov/pubmed/36466087
http://dx.doi.org/10.1155/2022/9197940
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