Lung transplant failure within the first 72 hours — called primary graft dysfunction (PGD) — kills thousands of patients yearly. Researchers used single-cell RNA sequencing and spatial transcriptomics in mouse models to identify CD177+ neutrophils as the key inflammatory culprit. These cells show abnormally high mitochondrial complex I activity driving oxidative phosphorylation, ROS production, and neutrophil extracellular trap (NET) formation. In human lung transplant recipients, a rise in blood CD177+ neutrophils within 4 hours post-transplant strongly predicted severe PGD (AUC=0.871). Blocking mitochondrial complex I with the drug IACS-010759 significantly reduced lung injury in both mouse and rat transplant models, opening a realistic path toward early diagnosis and targeted treatment of this devastating complication.
