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Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation
Intracellular adenosine monophosphate (AMP) is indispensable for cellular metabolic processes, and it is interconverted to ADP and/or ATP or activates AMP-activated protein kinase (AMPK). However, the specific biological function of extracellular AMP has not been identified. We evaluated the effect...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358592/ https://www.ncbi.nlm.nih.gov/pubmed/32733440 http://dx.doi.org/10.3389/fimmu.2020.01220 |
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author | Hua, Ye Liu, Dadong Zhang, Danyi Wang, Xu Wei, Qing Qin, Weiting |
author_facet | Hua, Ye Liu, Dadong Zhang, Danyi Wang, Xu Wei, Qing Qin, Weiting |
author_sort | Hua, Ye |
collection | PubMed |
description | Intracellular adenosine monophosphate (AMP) is indispensable for cellular metabolic processes, and it is interconverted to ADP and/or ATP or activates AMP-activated protein kinase (AMPK). However, the specific biological function of extracellular AMP has not been identified. We evaluated the effect of extracellular AMP using in vivo and in vitro models of endotoxemia. We found that AMP inhibited inflammation and neutrophil activation in lipopolysaccharide (LPS)-induced endotoxemic mice. The effects of extracellular AMP were abolished by an adenosine 1 receptor (A1R) antagonist but were not influenced by inhibiting the conversion of AMP to adenosine (ADO), indicating that AMP inhibited inflammation by directly activating A1R. In addition, in vitro experiments using LPS-stimulated mouse neutrophils showed that AMP inhibited LPS-induced reactive oxygen species (ROS) production, degranulation, and cytokine production, while the effects were reversed by an A1R antagonist. Further research showed that AMP regulated LPS-stimulated neutrophil functions by inhibiting the p38 MAPK pathway. These findings were also confirmed in primary neutrophils derived from healthy human blood. Moreover, we collected serum samples from septic patients. We found that AMP levels were increased compared with those of healthy volunteers and that AMP levels were negatively correlated with disease severity. Together, these data provide evidence that extracellular AMP acts on A1R to suppress endotoxemia-induced inflammation by inhibiting neutrophil overactivation and that the p38 MAPK signaling pathway is involved. |
format | Online Article Text |
id | pubmed-7358592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73585922020-07-29 Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation Hua, Ye Liu, Dadong Zhang, Danyi Wang, Xu Wei, Qing Qin, Weiting Front Immunol Immunology Intracellular adenosine monophosphate (AMP) is indispensable for cellular metabolic processes, and it is interconverted to ADP and/or ATP or activates AMP-activated protein kinase (AMPK). However, the specific biological function of extracellular AMP has not been identified. We evaluated the effect of extracellular AMP using in vivo and in vitro models of endotoxemia. We found that AMP inhibited inflammation and neutrophil activation in lipopolysaccharide (LPS)-induced endotoxemic mice. The effects of extracellular AMP were abolished by an adenosine 1 receptor (A1R) antagonist but were not influenced by inhibiting the conversion of AMP to adenosine (ADO), indicating that AMP inhibited inflammation by directly activating A1R. In addition, in vitro experiments using LPS-stimulated mouse neutrophils showed that AMP inhibited LPS-induced reactive oxygen species (ROS) production, degranulation, and cytokine production, while the effects were reversed by an A1R antagonist. Further research showed that AMP regulated LPS-stimulated neutrophil functions by inhibiting the p38 MAPK pathway. These findings were also confirmed in primary neutrophils derived from healthy human blood. Moreover, we collected serum samples from septic patients. We found that AMP levels were increased compared with those of healthy volunteers and that AMP levels were negatively correlated with disease severity. Together, these data provide evidence that extracellular AMP acts on A1R to suppress endotoxemia-induced inflammation by inhibiting neutrophil overactivation and that the p38 MAPK signaling pathway is involved. Frontiers Media S.A. 2020-07-07 /pmc/articles/PMC7358592/ /pubmed/32733440 http://dx.doi.org/10.3389/fimmu.2020.01220 Text en Copyright © 2020 Hua, Liu, Zhang, Wang, Wei and Qin. http://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 Hua, Ye Liu, Dadong Zhang, Danyi Wang, Xu Wei, Qing Qin, Weiting Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title | Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title_full | Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title_fullStr | Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title_full_unstemmed | Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title_short | Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation |
title_sort | extracellular amp suppresses endotoxemia-induced inflammation by alleviating neutrophil activation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358592/ https://www.ncbi.nlm.nih.gov/pubmed/32733440 http://dx.doi.org/10.3389/fimmu.2020.01220 |
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