Neutrophil Traps Drive Reperfusion Injury Across Organs

A new comprehensive review published in Burns & Trauma reveals that neutrophils and their web-like structures, known as neutrophil extracellular traps (NETs), are key drivers of the paradoxical damage that occurs when blood flow is restored after a heart attack, stroke, or severe injury. This phenomenon, called ischaemia–reperfusion injury (IRI), affects millions of patients worldwide and can worsen outcomes despite successful vessel reopening. The review, led by researchers from Chongqing University Central Hospital, University Hospital Essen, and Ludwig-Maximilians-University Munich, systematically examines how NETs intensify inflammation, block microvessels, and damage endothelial barriers across multiple organs including the heart, brain, kidney, liver, and lung.

The review highlights that NETs are not uniformly harmful; their effects depend on the specific organ, disease stage, and local microenvironment. In the heart, NETs can worsen cardiomyocyte injury and post-reperfusion inflammation. In the brain, NET accumulation may obstruct cerebral microvessels and disrupt the blood–brain barrier, contributing to poor neurological recovery even when the vessel is reopened. The review also introduces the concept of the "NET–organ axis," where NET-driven inflammation and thrombosis can extend damage beyond the original injury site, potentially leading to multiple organ dysfunction syndrome (MODS). Biomarkers such as cell-free DNA (cfDNA), citrullinated histone H3 (CitH3), and myeloperoxidase–DNA (MPO–DNA) complexes are discussed as promising tools for monitoring disease severity and therapeutic response.

The authors emphasize that the therapeutic goal should not be to eliminate neutrophil function entirely, but to identify when NET formation becomes excessive and how it can be safely controlled. Potential strategies include limiting harmful neutrophil recruitment, blocking PAD4-dependent NET formation, reducing ROS-driven activation, and accelerating NET clearance with DNase I-based therapies. However, clinical translation will require organ-specific biomarkers, careful timing, and strong safety evaluation because NETs also support antimicrobial defense. This research was supported by the Natural Science Foundation of Chongqing and the National Natural Science Foundation of China, and it points toward more precise, stage-specific interventions for reducing reperfusion-related injury in cardiovascular disease, stroke, transplantation, and critical care.