%0 Journal Article
%T HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke.
%A Yu C
%A Huang Y
%A Xie J
%A Duan C
%A Liu S
%A Zhao W
%A Wang Y
%A Zhuang R
%A Li J
%A Yin W
%J Int J Hyperthermia
%V 41
%N 1
%D 2024
%M 39117343
%F 3.753
%R 10.1080/02656736.2024.2378867
%X <B>UNASSIGNED: </B>Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.<BR><B>UNASSIGNED: </B>Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.<BR><B>UNASSIGNED: </B>Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.<BR><B>UNASSIGNED: </B>The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.