Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing Medical University, Nanjing, Jiangsu, China.
Center of Severe Acute Pancreatitis (CSAP), Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Int Immunopharmacol. 2023 Oct;123:110737. doi: 10.1016/j.intimp.2023.110737. Epub 2023 Aug 3.
CXCR4 neutrophils, which are a subset of neutrophils with high CXCR4 expression, are important contributors to sepsis-induced acute lung injury (ALI). PFKFB3, a key glycolysis gene, plays an essential role in neutrophil inflammatory activation. However, the specific involvement of PFKFB3 in sepsis-induced ALI remains unclear. Here, we observed that PFKFB3 was upregulated in CXCR4 neutrophils and facilitated sepsis-induced ALI. Mechanistically, we observed that PFKFB3 promoted sepsis-induced ALI by enhancing neutrophil extracellular trap (NET) formation by CXCR4 neutrophils. Further study indicated that PFKFB3 promoted NET formation by upregulating glycolytic metabolism in CXCR4 neutrophils. In summary, our study uncovered a new mechanism by which CXCR4 neutrophils trigger sepsis-induced ALI by promoting NET formation, which is supported by PFKFB3-mediated glycolytic metabolism.
高表达 CXCR4 的中性粒细胞亚群 CXCR4 中性粒细胞是脓毒症诱导的急性肺损伤（ALI）的重要贡献者。PFKFB3 是糖酵解的关键基因，在中性粒细胞炎症激活中发挥重要作用。然而，PFKFB3 在脓毒症诱导的 ALI 中的具体作用尚不清楚。在这里，我们观察到 PFKFB3 在 CXCR4 中性粒细胞中上调，并促进脓毒症诱导的 ALI。在机制上，我们观察到 PFKFB3 通过增强 CXCR4 中性粒细胞的中性粒细胞胞外诱捕网（NET）形成来促进脓毒症诱导的 ALI。进一步的研究表明，PFKFB3 通过上调 CXCR4 中性粒细胞中的糖酵解代谢来促进 NET 形成。总之，我们的研究揭示了一种新的机制，即 CXCR4 中性粒细胞通过促进 NET 形成引发脓毒症诱导的 ALI，该机制得到了 PFKFB3 介导的糖酵解代谢的支持。
