Extracellular vesicle-packaged GBP2 from macrophages aggravates sepsis-induced acute lung injury by promoting ferroptosis in pulmonary vascular endothelial cells.

ABSTRACT: Macrophages play a critical role in the development of sepsis-induced acute lung injury (si-ALI), with extracellular vesicles (EVs) acting as crucial mediators. However, the effects and mechanisms of macrophage-derived EVs on si-ALI remain unclear. This study demonstrated that macrophage-derived EVs induce endothelial ferroptosis and barrier disruption during sepsis. Through proteomic sequencing and reanalysis of transcriptomic and single-cell sequencing data, guanylate-binding protein 2 (GBP2) was identified as a key EV molecule. Elevated GBP2 expression was observed in EVs and monocytes from the peripheral blood of sepsis patients, in LPS-stimulated THP-1 and RAW264.7 cells and their secreted EVs, and in macrophages within the lungs of CLP mice. Additionally, GBP2 expression in EVs showe

SUBMITTER: Li Z 

PROVIDER: S-EPMC11994402 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature