Neutrophil extracellular traps mediate inflammation and coagulation dysregulation in primary blast lung injury

Xiangyan Meng; Junfeng Li; Qianying Lu; Jianfeng Zhang; Yi Zheng; Ziquan Liu; Mengjun Ji; Zihan Kou; Linlin Li; Haojun Fan

doi:10.1016/j.bcp.2025.117149

Neutrophil extracellular traps mediate inflammation and coagulation dysregulation in primary blast lung injury

Biochem Pharmacol. 2025 Jul 11:117149. doi: 10.1016/j.bcp.2025.117149. Online ahead of print.

Authors

Xiangyan Meng¹, Junfeng Li², Qianying Lu¹, Jianfeng Zhang³, Yi Zheng¹, Ziquan Liu¹, Mengjun Ji², Zihan Kou², Linlin Li², Haojun Fan⁴

Affiliations

¹ School of Disaster and Emergency Medicine, Tianjin University, 300072, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China; Key Laboratory of Emergency Management Department, Tianjin 300072, China.
² School of Disaster and Emergency Medicine, Tianjin University, 300072, China; Key Laboratory of Emergency Management Department, Tianjin 300072, China.
³ Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China; Key Laboratory of Emergency Management Department, Tianjin 300072, China.
⁴ School of Disaster and Emergency Medicine, Tianjin University, 300072, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China; Key Laboratory of Emergency Management Department, Tianjin 300072, China. Electronic address: haojunfan86@163.com.

PMID: 40653027
DOI: 10.1016/j.bcp.2025.117149

Abstract

Primary blast lung injury (PBLI) manifests as respiratory distress and hemoptysis syndrome resulting from exposure to blast waves, yet its pathogenesis remains incompletely understood, leading to a dearth of effective treatment options. Neutrophil extracellular traps (NETs) may play important roles in acute lung injury. However, the role of NETs in PBLI was unclear. Therefore, the objective of the present study was to investigate the role of NETs in PBLI. Our study found that, compared to the Con group, blast wave induced the destruction of lung tissue structure, the increase of lung inflammatory factors, coagulation-related factors, and endothelial injury markers, as well as the release of NETs. Further research showed that the levels of inflammatory factors, coagulation-related factors, and endothelial injury markers of pulmonary microvascular endothelial cells (PMVEC) were up-regulated after co-culturing with neutrophils extracted from the blood of PBLI rats, compared to the Con group. The damaging effect of NETs on the lung tissue of rats and PMVEC was reversed after DNase I was applied. Our work revealed that blast exposure induces lung tissue inflammation and coagulation disorders in PBLI rats by mediating PMVEC dysfunction, thereby accelerating the development of PBLI. Moreover, NETs are the key factors causing inflammation and coagulation disorders of PBLI, and the elimination of NETs may become a new target for PBLI therapy.

Keywords: Acute lung injury; Blast injury; Coagulation; DNase I; Inflammation; Neutrophil extracellular traps.