Sepsis-secreted G6PD supports guanine generation and Histone H3K27 demethylation to drive inflammatory macrophages

Sepsis is a complex syndrome associated with physiological, pathological, and biochemical abnormalities resulting from infection. Sepsis is the major cause of acute respiratory distress syndrome (ARDS). Extracellular vesicles (EVs) are serving as new messengers to mediate cell-cell communication in vivo. The function of EVs in sepsis patients are not well defined. We found sepsis EV encapsulating G6PD induced pro-inflammatory effects in the lung tissue by reprogramming purine metabolism. Most notably, guanine accumulation led to EZH2-mediated H3K27Me3 level. Finally Our study provides a novel mechanism of how EV reviried puring metabolism in lung tissue and leading to acute lung damage. Overall design: Comparative gene expression profiling analysis of RNA-seq data for C57BL/6 lung established by Sham, CLP (cecal ligation and puncture), CLP+GW.