A comprehensive review published in Burns & Trauma on 15 June 2026 brings together evidence that neutrophils and the web-like structures they release, known as neutrophil extracellular traps (NETs), are central players in ischaemia–reperfusion injury (IRI). IRI is a shared pathological process in myocardial infarction, ischaemic stroke, acute kidney injury, lung injury, and graft dysfunction after transplantation. Although rapid reperfusion remains essential for tissue survival, sudden oxygen restoration can activate sterile inflammation, reactive oxygen species production, endothelial dysfunction, and immunothrombosis.
The review, conducted by researchers from Chongqing University Central Hospital, Chongqing University, University Hospital Essen, University of Duisburg-Essen, and Ludwig-Maximilians-University Munich (DOI: 10.1093/burnst/tkag022), systematically examines how neutrophils and NETs contribute to IRI across the heart, brain, kidney, liver, lung, and transplanted organs. Activated neutrophils release NETs composed of decondensed DNA, histones, myeloperoxidase (MPO), neutrophil elastase (NE), and other granular proteins. While NETs help trap microbes during infection, excessive NET formation in sterile injury can damage endothelial cells, promote microthrombus formation, and sustain inflammatory feedback loops.
A key strength of the review is its cross-organ perspective. In the heart, NETs can worsen cardiomyocyte injury and post-reperfusion inflammation. In the brain, NET accumulation may obstruct cerebral microvessels, disrupt the blood–brain barrier, and contribute to the mismatch between successful vessel reopening and poor neurological recovery. In the kidney and liver, NETs interact with tubular cells, hepatocytes, Kupffer cells, and sinusoidal endothelial cells, amplifying inflammation and graft dysfunction. The review also discusses the "NET–organ axis," in which NET-driven inflammation and thrombosis extend damage beyond the original injury site and contribute to multiple organ dysfunction syndrome (MODS).
Biomarkers such as cell-free DNA (cfDNA), citrullinated histone H3 (CitH3), and MPO–DNA complexes may help monitor disease severity and therapeutic response. The authors said the review highlights NETs as dynamic immune structures rather than simple inflammatory debris. Their effects depend on timing, tissue context, and the balance between host defense and tissue damage. The therapeutic goal should not be to eliminate neutrophil function entirely, but to identify when NET formation becomes excessive, where it causes the greatest harm, and how it can be safely controlled.
Potential therapeutic approaches include limiting harmful neutrophil recruitment, blocking peptidyl arginine deiminase 4 (PAD4)-dependent NET formation, reducing ROS-driven activation, modulating complement-related pathways, and accelerating NET clearance with deoxyribonuclease I (DNase I)-based therapies. However, clinical translation will require organ-specific biomarkers, careful timing, and strong safety evaluation, because NETs also support antimicrobial defense. With better patient stratification, NET-targeted therapies may offer a practical route to protecting organs after reperfusion.
The research was funded by the Natural Science Foundation of Chongqing, China (Grant No. CSTB2025NSCQ-GPX1056); Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202300114); National Natural Science Foundation of China (Grant Nos. 82500355 and 81900381); and 2023 Key Disciplines on Public Health Construction in Chongqing.
