From Bench to Bedside: Implications and Interventions for Endotoxin Exposure in Lipopolysaccharide-Induced Apoptosis and Eryptosis

Lipopolysaccharide, a key component of Gram-negative bacterial membranes, initiates potent inflammatory responses through both Toll-like receptor 4-dependent and -independent pathways. Beyond cytokine-driven immune activation, LPS orchestrates cell death programs across diverse cell types, notably apoptosis in nucleated cells and eryptosis in erythrocytes. These processes share convergent stress signals but different mechanisms. Experimental models demonstrate that LPS, particularly in the presence of immune cells, induces erythrocyte death through oxidative injury, calcium influx, and membrane remodeling, culminating in PS exposure and microparticle formation, reflecting clinical patterns seen in patients with sepsis. Diagnostic tools, such as the Endotoxin Activity Assay, enable risk stratification and enrichment for interventional trials in this population. Recent evidence from trials suggests that targeted hemoadsorption therapies may benefit select patients with LPS exposure and these pathophysiological features. This review integrates pathophysiology, diagnostic, and therapeutic insights to highlight eryptosis as both a biomarker and mediator of inflammatory injury, offering novel mechanisms for intervention in critical illness.