Cargando…

The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis

The cholinergic anti-inflammatory pathway has been identified as an effective pathway to modify inflammatory responses. Here, we verified that delayed administration with a selective α7nAChR agonist GTS-21 enables a more efficient elimination of the offending pathogens, diminished inflammatory respo...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Jian-nan, Liu, Ying, Liu, Shu-chang, Zhang, Teng, Chen, Gui-bing, Zhao, Jie, Ma, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931331/
https://www.ncbi.nlm.nih.gov/pubmed/35309361
http://dx.doi.org/10.3389/fimmu.2022.839290
_version_ 1784671235317170176
author Hu, Jian-nan
Liu, Ying
Liu, Shu-chang
Zhang, Teng
Chen, Gui-bing
Zhao, Jie
Ma, Tao
author_facet Hu, Jian-nan
Liu, Ying
Liu, Shu-chang
Zhang, Teng
Chen, Gui-bing
Zhao, Jie
Ma, Tao
author_sort Hu, Jian-nan
collection PubMed
description The cholinergic anti-inflammatory pathway has been identified as an effective pathway to modify inflammatory responses. Here, we verified that delayed administration with a selective α7nAChR agonist GTS-21 enables a more efficient elimination of the offending pathogens, diminished inflammatory response and organ injury, and improved survival rates in the polymicrobial septic peritonitis model. We illustrated that the improved bacterial clearance upon GTS-21 stimulation was accompanied by enhanced recruitment of monocytes into the peritoneal cavity and simultaneously increased phagocytic activity and iNOS expression of these recruited monocytes. Mechanically, splenectomy prior to administration of GTS-21 attenuated the recruitment of monocytes into the peritoneal cavity and abolished the protective benefits of GTS-21 treatment. Meanwhile, GTS-21 administration accelerates the deployment of splenic monocytes during septic peritonitis. Collectively, these data suggested that appropriate selective pharmacological α7nAChR activation promotes monocytes trafficking in a spleen-dependent manner and upregulates the antibacterial activity of recruited monocytes during septic peritonitis, which may be utilized as a promising therapeutic modality for patients suffering from septic peritonitis.
format Online
Article
Text
id pubmed-8931331
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89313312022-03-19 The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis Hu, Jian-nan Liu, Ying Liu, Shu-chang Zhang, Teng Chen, Gui-bing Zhao, Jie Ma, Tao Front Immunol Immunology The cholinergic anti-inflammatory pathway has been identified as an effective pathway to modify inflammatory responses. Here, we verified that delayed administration with a selective α7nAChR agonist GTS-21 enables a more efficient elimination of the offending pathogens, diminished inflammatory response and organ injury, and improved survival rates in the polymicrobial septic peritonitis model. We illustrated that the improved bacterial clearance upon GTS-21 stimulation was accompanied by enhanced recruitment of monocytes into the peritoneal cavity and simultaneously increased phagocytic activity and iNOS expression of these recruited monocytes. Mechanically, splenectomy prior to administration of GTS-21 attenuated the recruitment of monocytes into the peritoneal cavity and abolished the protective benefits of GTS-21 treatment. Meanwhile, GTS-21 administration accelerates the deployment of splenic monocytes during septic peritonitis. Collectively, these data suggested that appropriate selective pharmacological α7nAChR activation promotes monocytes trafficking in a spleen-dependent manner and upregulates the antibacterial activity of recruited monocytes during septic peritonitis, which may be utilized as a promising therapeutic modality for patients suffering from septic peritonitis. Frontiers Media S.A. 2022-03-04 /pmc/articles/PMC8931331/ /pubmed/35309361 http://dx.doi.org/10.3389/fimmu.2022.839290 Text en Copyright © 2022 Hu, Liu, Liu, Zhang, Chen, Zhao and Ma 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
Hu, Jian-nan
Liu, Ying
Liu, Shu-chang
Zhang, Teng
Chen, Gui-bing
Zhao, Jie
Ma, Tao
The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title_full The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title_fullStr The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title_full_unstemmed The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title_short The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
title_sort α7 nicotinic acetylcholine receptor agonist gts-21 improves bacterial clearance via regulation of monocyte recruitment and activity in polymicrobial septic peritonitis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931331/
https://www.ncbi.nlm.nih.gov/pubmed/35309361
http://dx.doi.org/10.3389/fimmu.2022.839290
work_keys_str_mv AT hujiannan thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT liuying thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT liushuchang thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT zhangteng thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT chenguibing thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT zhaojie thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT matao thea7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT hujiannan a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT liuying a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT liushuchang a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT zhangteng a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT chenguibing a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT zhaojie a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis
AT matao a7nicotinicacetylcholinereceptoragonistgts21improvesbacterialclearanceviaregulationofmonocyterecruitmentandactivityinpolymicrobialsepticperitonitis