Therapeutic Galectin-3 Apheresis Improves Sepsis Outcomes Through Coordinated Neutrophil Modulation and Endothelial Barrier Preservation: A Translational Study

Abstract

Sepsis remains a leading cause of global mortality, characterized by uncontrolled inflammation and multi-organ dysfunction. Galectin-3 (Gal-3) is a damage-associated molecular pattern (DAMP) protein that amplifies inflammatory cascades during sepsis and represents a potential therapeutic target. We conducted an integrated translational investigation combining clinical observation (87 septic patients, 27 healthy volunteers) with preclinical Gal-3 removal using an anti-Gal-3 apheresis column in two sepsis models: a rat cecal ligation and puncture (CLP) model (n = 48) and a porcine lipopolysaccharide (LPS)-induced model (n = 31). Mechanistic assessments included serum testing, multi-omics profiling, invasive hemodynamic monitoring, and histopathology. Patients with sepsis exhibited markedly elevated Gal-3 levels (p < 0.001), and survivors showed progressive Gal-3 decline compared with non-survivors (p < 0.01). Gal-3 removal significantly improved survival in rats (57.1% vs. 25.0%, p = 0.003) and pigs (68.8% vs. 26.7%, p = 0.004). Treatment attenuated neutrophil activation and tissue infiltration, preserved endothelial barrier integrity, and modulated pro-survival and hypoxia-response signaling pathways, accompanied by reduced vasopressor requirements and pulmonary edema. Collectively, these findings demonstrate that Gal-3 removal improves survival and reduces organ damage in preclinical sepsis models in association with coordinated neutrophil modulation and endothelial barrier preservation, highlighting Gal-3 as a promising therapeutic target in sepsis.

Keywords

extracorporeal therapy / Galectin-3 / organ dysfunction / sepsis / survival

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