Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
J Clin Invest. 2023 Feb 1;133(3):e167012. doi: 10.1172/JCI167012.
Liver transplantation can be a life-saving treatment for end-stage hepatic disease. Unfortunately, some recipients develop ischemia-reperfusion injury (IRI) that leads to poor short- and long-term outcomes. Recent work has shown neutrophils contribute to IRI by undergoing NETosis, a form of death characterized by DNA ejection resulting in inflammatory extracellular traps. In this issue of the JCI, Hirao and Kojima et al. report that sphingosine-1-phosphate (S1P) expression induced by liver transplant-mediated IRI triggers NETosis. They also provide evidence that neutrophil expression of the carcinoembryonic antigen-related cell adhesion molecule-1 (CC1) long isoform inhibited NETosis by controlling S1P receptor-mediated autophagic flux. These findings suggest stimulating regulatory mechanisms that suppress NETosis could be used to prevent IRI.
肝移植可以成为治疗终末期肝病的一种救命疗法。不幸的是，一些接受者会出现缺血再灌注损伤（IRI），导致短期和长期预后不良。最近的研究表明，中性粒细胞通过 NETosis 导致 IRI，NETosis 是一种以 DNA 排出导致炎症性细胞外陷阱为特征的死亡形式。在本期 JCI 中，Hirao 和 Kojima 等人报告称，肝移植介导的 IRI 诱导的鞘氨醇-1-磷酸（S1P）表达触发 NETosis。他们还提供了证据表明，中性粒细胞表达癌胚抗原相关细胞黏附分子-1（CC1）长型异构体通过控制 S1P 受体介导的自噬通量来抑制 NETosis。这些发现表明，刺激抑制 NETosis 的调节机制可用于预防 IRI。
