Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , |
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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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 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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reponame:Repositório Institucional da UFOP instname:Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
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Universidade Federal de Ouro Preto (UFOP) |
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UFOP |
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Repositório Institucional da UFOP |
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Repositório Institucional da UFOP |
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Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP) |
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repositorio@ufop.edu.br |
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1813002864271818752 |