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Although timely reperfusion is indispensable for tissue salvage, it paradoxically promotes maladaptive immune activation and oxidative stress, which aggravate microvascular dysfunction and organ failure. Accumulating evidence indicates that sterile inflammation, endothelial injury, and immunothrombosis are the central drivers of IRI progression. Among innate immune effectors, neutrophils act as first responders that integrate chemotactic signalling, adhesion cascades, and metabolic rewiring. Upon activation, neutrophils release damage-associated molecular patterns and form neutrophil extracellular traps (NETs), which amplify inflammation, promote coagulation, and disrupt tissue repair across organs. However, the organ-specific roles, temporal dynamics, and translational relevance of neutrophils and NETs in IRI remain incompletely understood. In this review, we systematically dissect the neutrophil- and NET-mediated mechanisms involved in IRI across the heart, brain, kidney, liver, and transplanted organs, with a particular emphasis on endothelial crosstalk, immunothrombosis, and metabolic regulation. We further summarize emerging NET-associated biomarkers\u2014including cell-free DNA and myeloperoxidase\u2013DNA complexes\u2014for IRI diagnosis and prognosis. Finally, we evaluate therapeutic strategies targeting neutrophil recruitment, immune metabolism, and NET clearance, highlighting challenges for clinical translation. In summary, this review provides a mechanistic and translational framework for targeting neutrophils and NETs in precision therapies for IRI.<\/jats:p>","DOI":"10.1093\/burnst\/tkag022","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:36:48Z","timestamp":1773491808000},"source":"Crossref","is-referenced-by-count":2,"title":["Neutrophils and neutrophil extracellular traps in ischaemia\u2013reperfusion injury: pathophysiological roles and therapeutic potential"],"prefix":"10.1093","volume":"14","author":[{"given":"Yiqiong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center), School of Medicine, Chongqing University , No. 1 Jiankang Road, Yuzhong District, 400014 Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center), School of Medicine, Chongqing University , No. 1 Jiankang Road, Yuzhong District, 400014 Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center), School of Medicine, Chongqing University , No. 1 Jiankang Road, Yuzhong District, 400014 Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Essen, University of Duisburg-Essen , Hufelandstra\u00dfe 55, 45147 Essen, North Rhine-Westphalia,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center), School of Medicine, Chongqing University , No. 1 Jiankang Road, Yuzhong District, 400014 Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center), School of Medicine, Chongqing University , No. 1 Jiankang Road, Yuzhong District, 400014 Chongqing 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