Pentraxin‐related protein <scp>PTX3</scp> alleviates blast‐induced acute lung injury by promoting efferocytosis to eliminate ferroptotic alveolar epithelial cells in vitro

Blast injuries are common in both peacetime and war, and one of the main types is lung injury, characterised by internal severity, rapid changes in condition, high mortality, and complex injury patterns. The primary pathological manifestation is pulmonary haemorrhage caused by damage to alveolar epithelial cells (AECs) and capillary endothelial cells. Treatment is complex, making it essential to fully understand the characteristics and pathogenesis of blast-induced acute lung injury (bALI) to improve treatment efficacy. In this study, a rat blast-injury model was established through a fuel-air explosion, and significant injury to the lungs and AECs was detected. Transcriptome sequencing analysis showed that ferroptosis and efferocytosis are significant in bALI; among several common lung injury biomarkers, pentraxin-related protein PTX3 was significantly increased, which was further confirmed by subsequent experiments. Additionally, to study AEC injury, we treated cells with extracts from the lung tissue of bALI rats undergoing in vitro simulation experiments, confirming the injury of AECs and ferroptosis with an increase in PTX3. As an important mediator of inflammation and a biomarker significantly increased in many ALIs, the role of PTX3 in ALI remains poorly understood. In this study, we detected increased efferocytosis efficiency of alveolar macrophages in ferroptotic AECs by increasing endogenous PTX3 expression. These findings are of great significance for the clearance of low-efficiency ferroptotic cells, as they can reduce the efferocytosis burden on alveolar macrophages, mitigate secondary lung injury, and may provide new molecular insights for delaying the progression of bALI and improving treatment.