Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.

Detalhes bibliográficos
Autor(a) principal: Silva, Juliana Priscila Vago da
Data de Publicação: 2023
Outros Autores: Zaidan, Isabella, Perucci, Luiza Oliveira, Brito, Larissa Froede, Teixeira, Lívia Cristina Ribeiro, Silva, Camila Meirelles Souza, Miranda, Thaís Cristina de, Melo, Eliza Mathias, Bruno, Alexandre Santos, Queiroz Júnior, Celso Martins, Sugimoto, Michelle Adriane Amantéa, Tavares, Luciana Padua, Ferreira, Lais Cunha Grossi, Borges, Isabela Nascimento, Schneider, Ayda Henriques, Baik, Nagyung, Silva, André Talvani Pedrosa da, Ferreira, Raphael Gomes, Alves Filho, José Carlos Farias, Nobre Junior, Vandack Alencar, Teixeira, Mauro Martins, Parmer, Robert J., Miles, Lindsey A., Sousa, Lirlândia Pires de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFOP
Texto Completo: http://www.repositorio.ufop.br/jspui/handle/123456789/17692
https://doi.org/10.1172/jci.insight.166044
Resumo: Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla– afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.
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spelling Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla– afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.2023-10-31T19:10:20Z2023-10-31T19:10:20Z2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfSILVA, J. P. V. da et al. Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation. JCI Insight, v. 14, artigo e166044, 2023. Disponível em: <https://insight.jci.org/articles/view/166044/pdf>. Acesso em: 01 ago. 2023.2379-3708http://www.repositorio.ufop.br/jspui/handle/123456789/17692https://doi.org/10.1172/jci.insight.166044This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Fonte: PDF do artigo.info:eu-repo/semantics/openAccessSilva, Juliana Priscila Vago daZaidan, IsabellaPerucci, Luiza OliveiraBrito, Larissa FroedeTeixeira, Lívia Cristina RibeiroSilva, Camila Meirelles SouzaMiranda, Thaís Cristina deMelo, Eliza MathiasBruno, Alexandre SantosQueiroz Júnior, Celso MartinsSugimoto, Michelle Adriane AmantéaTavares, Luciana PaduaFerreira, Lais Cunha GrossiBorges, Isabela NascimentoSchneider, Ayda HenriquesBaik, NagyungSilva, André Talvani Pedrosa daFerreira, Raphael GomesAlves Filho, José Carlos FariasNobre Junior, Vandack AlencarTeixeira, Mauro MartinsParmer, Robert J.Miles, Lindsey A.Sousa, Lirlândia Pires deengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOP2024-01-31T17:45:24Zoai:repositorio.ufop.br:123456789/17692Repositório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332024-01-31T17:45:24Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false
dc.title.none.fl_str_mv Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
title Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
spellingShingle Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
Silva, Juliana Priscila Vago da
title_short Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
title_full Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
title_fullStr Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
title_full_unstemmed Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
title_sort Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
author Silva, Juliana Priscila Vago da
author_facet Silva, Juliana Priscila Vago da
Zaidan, Isabella
Perucci, Luiza Oliveira
Brito, Larissa Froede
Teixeira, Lívia Cristina Ribeiro
Silva, Camila Meirelles Souza
Miranda, Thaís Cristina de
Melo, Eliza Mathias
Bruno, Alexandre Santos
Queiroz Júnior, Celso Martins
Sugimoto, Michelle Adriane Amantéa
Tavares, Luciana Padua
Ferreira, Lais Cunha Grossi
Borges, Isabela Nascimento
Schneider, Ayda Henriques
Baik, Nagyung
Silva, André Talvani Pedrosa da
Ferreira, Raphael Gomes
Alves Filho, José Carlos Farias
Nobre Junior, Vandack Alencar
Teixeira, Mauro Martins
Parmer, Robert J.
Miles, Lindsey A.
Sousa, Lirlândia Pires de
author_role author
author2 Zaidan, Isabella
Perucci, Luiza Oliveira
Brito, Larissa Froede
Teixeira, Lívia Cristina Ribeiro
Silva, Camila Meirelles Souza
Miranda, Thaís Cristina de
Melo, Eliza Mathias
Bruno, Alexandre Santos
Queiroz Júnior, Celso Martins
Sugimoto, Michelle Adriane Amantéa
Tavares, Luciana Padua
Ferreira, Lais Cunha Grossi
Borges, Isabela Nascimento
Schneider, Ayda Henriques
Baik, Nagyung
Silva, André Talvani Pedrosa da
Ferreira, Raphael Gomes
Alves Filho, José Carlos Farias
Nobre Junior, Vandack Alencar
Teixeira, Mauro Martins
Parmer, Robert J.
Miles, Lindsey A.
Sousa, Lirlândia Pires de
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silva, Juliana Priscila Vago da
Zaidan, Isabella
Perucci, Luiza Oliveira
Brito, Larissa Froede
Teixeira, Lívia Cristina Ribeiro
Silva, Camila Meirelles Souza
Miranda, Thaís Cristina de
Melo, Eliza Mathias
Bruno, Alexandre Santos
Queiroz Júnior, Celso Martins
Sugimoto, Michelle Adriane Amantéa
Tavares, Luciana Padua
Ferreira, Lais Cunha Grossi
Borges, Isabela Nascimento
Schneider, Ayda Henriques
Baik, Nagyung
Silva, André Talvani Pedrosa da
Ferreira, Raphael Gomes
Alves Filho, José Carlos Farias
Nobre Junior, Vandack Alencar
Teixeira, Mauro Martins
Parmer, Robert J.
Miles, Lindsey A.
Sousa, Lirlândia Pires de
description Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla– afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.
publishDate 2023
dc.date.none.fl_str_mv 2023-10-31T19:10:20Z
2023-10-31T19:10:20Z
2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv SILVA, J. P. V. da et al. Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation. JCI Insight, v. 14, artigo e166044, 2023. Disponível em: <https://insight.jci.org/articles/view/166044/pdf>. Acesso em: 01 ago. 2023.
2379-3708
http://www.repositorio.ufop.br/jspui/handle/123456789/17692
https://doi.org/10.1172/jci.insight.166044
identifier_str_mv SILVA, J. P. V. da et al. Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation. JCI Insight, v. 14, artigo e166044, 2023. Disponível em: <https://insight.jci.org/articles/view/166044/pdf>. Acesso em: 01 ago. 2023.
2379-3708
url http://www.repositorio.ufop.br/jspui/handle/123456789/17692
https://doi.org/10.1172/jci.insight.166044
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFOP
instname:Universidade Federal de Ouro Preto (UFOP)
instacron:UFOP
instname_str Universidade Federal de Ouro Preto (UFOP)
instacron_str UFOP
institution UFOP
reponame_str Repositório Institucional da UFOP
collection Repositório Institucional da UFOP
repository.name.fl_str_mv Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)
repository.mail.fl_str_mv repositorio@ufop.edu.br
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