Neutrophil extracellular traps facilitate liver inflammation/fibrosis progression by entering macrophages and triggering AIM2 inflammasome-dependent pyroptosis

作者：Yu Zhang, Yu Zhang, Rong Wu, Rong Wu, Xi Zhan, Xuanyi Wang, Lin-Wei Xiang, Ya-Qian Duan, Yan You, Yunyuan Zhang, Rui Wu, Rui Wu, Yunyuan Zhang, Yunyuan Zhang, Liang Duan · 发表于：Cell Communication and Signaling · 年份：2024 · DOI：10.1186/s12964-024-01944-9 · 被引用次数：30 · 研究领域：Inflammasome and immune disorders、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Liver Diseases and Immunity

BACKGROUND: Absent in melanoma 2 (AIM2) inflammasome-dependent pyroptosis and neutrophil extracellular traps (NETs) have been implicated in chronic liver disease (CLD). However, the specific intrahepatic cell type that undergoes AIM2 inflammasome-dependent pyroptosis and how their interaction augments hepatic inflammation/fibrosis remains unclear. METHODS: The expression and correlation of AIM2 inflammasome-dependent pyroptosis-related indicators and NETs were analyzed in biopsy tissue and blood specimens from chronic hepatitis patients (CHs). Cell-based experiments were conducted to investigate their interaction. In vitro and in vivo experiments were used to analyze their effects on the progression of hepatic inflammation/fibrosis as well as their clinical importance. RESULTS: Elevated levels of AIM2 inflammasome-dependent pyroptosis indicators and NETs were detected in biopsy tissue and blood specimens. Circulating NETs were positively correlated with pyroptosis-related indicators, and both were related with disease severity. Confocal imaging revealed that AIM2 was mainly localized to hepatic macrophages, indicating that hepatic macrophages were the major cell type that underwent pyroptosis. NETs were directly engulfed by macrophages and then stimulated AIM2 inflammasome-dependent macrophage pyroptosis in vitro, which amplified the activation of hepatic stellate cells (HSCs) and increased collagen deposition. Administration of the NETs degradation agent DNase I or the AIM2 ...