败血症
中性粒细胞胞外陷阱
炎症
全身炎症
免疫学
纤溶酶
纤溶
纤溶酶原激活剂
纤维蛋白
医学
HMGB1
纤溶酶原激活物抑制剂-1
弥漫性血管内凝血
生物
内科学
生物化学
酶
作者
Juliana P. Vago,Isabella Zaidan,Luíza Oliveira Perucci,Larissa Froede Brito,Lívia C.R. Teixeira,Camila Ms Silva,Thaís C. Miranda,Eliza Mathias Melo,Alexandre S Bruno,Celso Martins Queiroz-Júnior,Michelle A. Sugimoto,Luciana P. Tavares,Laís C. Grossi,Isabela N Borges,Nagyung Baik,André Talvani,Raphael Gomes Ferreira,José Carlos Alves‐Filho,Vandack Nobre,Mauro Martins Teixeira,Robert J. Parmer,Lindsey A. Miles,Lirlândia P. Sousa
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-04-24
卷期号:8 (8)
被引量:6
标识
DOI:10.1172/jci.insight.166044
摘要
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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