Extracellular vesicle-bound S100A8/A9 is differentially expressed in septic shock and prompts acute lung injury.
Summary
EV-bound S100A8/A9 is elevated in sepsis/septic shock, discriminates septic shock from sepsis, and predicts ARDS. Septic shock EVs induce acute lung injury via alveolar macrophage uptake and S100A8/A9–RAGE signaling; neutralizing S100A8/A9 or genetic RAGE deficiency attenuates injury.
Key Findings
- EV-bound S100A8/A9 levels are significantly higher in sepsis/septic shock than in healthy controls and discriminate septic shock from sepsis (ROC).
- Septic shock EVs induce acute lung injury and M1 macrophage polarization in mice independent of LPS.
- Neutralizing S100A8/A9 or RAGE deficiency attenuates EV-induced lung injury, implicating the S100A8/A9–RAGE axis.
Clinical Implications
EV S100A8/A9 could aid early risk stratification for ARDS in sepsis and guide trials of S100A8/A9 or RAGE blockade. It supports biomarker-driven enrollment and monitoring in precision critical care.
Why It Matters
Provides a mechanistic EV–alarmin pathway linking sepsis to lung injury and a clinically measurable biomarker with predictive value. It opens therapeutic avenues targeting S100A8/A9–RAGE.
Limitations
- Clinical sample size and external validation cohorts are not specified in the abstract.
- Translational study; no interventional clinical testing of S100A8/A9/RAGE blockade.
Future Directions
Validate EV S100A8/A9 thresholds in multicenter cohorts and test S100A8/A9 or RAGE-targeted interventions in preclinical and early-phase clinical trials.
Study Information
- Study Type
- Cohort
- Research Domain
- Pathophysiology
- Evidence Level
- V - Translational mechanistic study combining human samples and animal models without randomization.
- Study Design
- OTHER