Silva, 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 de2023-10-312023-10-312023SILVA, 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/123456789/17692Sepsis 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.en-USabertoArtigo publicado em periodicoThis is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Fonte: PDF do artigo.https://doi.org/10.1172/jci.insight.166044