Endotoxin-induced Ferroptosis-associated Leukocyte Injury and DAMP Release in Sepsis: An in Vitro Study

Background: Sepsis is characterized by dysregulated inflammation and thromboinflammation in which regulated cell death and damage-associated molecular patterns (DAMPs) contribute to organ injury. Ferroptosis has recently emerged as a potential mechanism of inflammatory cell injury in sepsis. Objective: endotoxin model. Methods: fluorescence probes. Cellular morphology was assessed using May-Grünwald-Giemsa staining, DAPI staining, and immunofluorescence for histone H3 and citrullinated histone H3. Results: accumulation, suggesting ferroptosis-associated iron dysregulation. DAPI staining showed chromatin injury and extracellular DNA release. Histone H3-positive and citrullinated histone H3-positive cells coexisted within the same inflammatory population, indicating overlap between inflammatory lytic cell death and NETosis-like responses. Conclusions: Ferroptosis-associated iron accumulation, DAMP release, and overlapping inflammatory cell death phenotypes may collectively contribute to thromboinflammation and organ injury in sepsis.