Macrophages-derived high-mobility group box-1 protein induces endothelial progenitor cells pyroptosis

Endothelial dysfunction is an important factor in the progress of sepsis. Endothelial progenitor cells (EPCs) are the precursor cells of endothelial cells and play a crucial role in the prognosis and treatment of sepsis. EPCs in the peripheral blood of patients with sepsis undergo pyroptosis, but the mechanism remains much of unknown. Serum high-mobility group box-1 (HMGB1) is significantly elevated in patients with sepsis, but whether it is related to EPCs pyroptosis is unknown. We used a cell model of sepsis in vitro to isolate EPCs for better observation. By detecting the pyroptosis-related indicators of EPCs and the level of release and acetylation of HMGB1 in inflammatory macrophages, it was found that HMGB1 released by inflammatory macrophages combined with receptor for advanced glycation end products (RAGE) is a key pathway to induce pyroptosis of EPCs. [Display omitted] •EPCs in peripheral blood of patients with sepsis undergo pyroptosis•Septic macrophages are associated with EPCs pyroptosis•EPCs in septic peripheral circulation undergo pyroptosis via the HMGB1/RAGE axis Pathophysiology; Immunology; Cell biology