Authors: Xuejing Sun, Sultan S. Abdelhamid, Zachary Secunda, Robert Voinchet, Alyssa Gregory, Jacob Scioscia, Mehves Ozel, Jennifer L. Darby, Hamed Moheimani, Qing-De Wang, Jishnu Das, Matthew D. Neal, Upendra K. Kar, Jason L. Sperry, Timothy R. Billiar
Published: 2025-05-28
DOI: 10.1126/scitranslmed.ado2622
Source: Full article
Severe injury accompanied by hemorrhagic shock triggers an early release of cell constituents into the circulation, referred to as the systemic storm. The systemic storm drives the systemic inflammatory response and is associated with increased mortality. The role of programmed cell death (PCD) in the systemic storm was investigated in mice that underwent hemorrhagic shock with tissue trauma (HS/T) followed by crystalloid resuscitation. Wild-type (WT) mice were treated with inhibitors, including z-VAD, necrostatin-1, ferrostatin-1, or disulfiram (DSF), to block the different forms of PCD. Gasdermin D (GSDMD)–dependent PCD was further targeted using