EMAP-II from macrophage-derived extracellular vesicles drives neutrophil extracellular traps formation via PI3K/AKT/mtROS in lung ischemia/reperfusion injury.

ABSTRACT: Lung ischemia/reperfusion injury (LIRI) is a significant complication following lung transplantation driven by neutrophil extracellular traps (NETs) associated with mitochondrial oxidative stress. However, the intercellular signaling mechanisms mediating oxidative stress remain unresolved. Here, we elucidated a mitochondrial reactive oxygen species (mtROS) amplification mechanism driven by extracellular vesicles (EVs). In this mechanism, EVs derived from oxygen-glucose deprivation/reperfusion (OGD/R)-activated macrophages transferred endothelial monocyte-activating polypeptide-II (EMAP-II) to neutrophils, suppressed PI3K/AKT signaling, and thereby induced mitochondrial oxidative stress that drove pathological NETs formation. Proteomic profiling identified EMAP-II as a key signaling molecul

SUBMITTER: Zhuang H 

PROVIDER: S-EPMC12271427 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature