Platelets Induce Neutrophil Extracellular Traps in Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality in the U.S. and a major cause of transfusion-associated morbidity including increased time on mechanical ventilation and length of stay in the intensive care unit and the hospital. Neutrophils have been identified as critical cellular mediators in the pathogenesis of TRALI in both clinical studies and in experimental settings using a variety of injury models. Platelets have been implicated as a blood product that can trigger TRALI, and endogenous platelet activation contributes to lung injury. Platelets bind to the surface of neutrophils to form heterotypic aggregates, and activated platelets can trigger the formation of neutrophil extracellular traps (NETs), which is a new mode of neutrophil death that is distinct from apoptosis and necrosis. NETs are produced in experimental TRALI and are increased in post-transfusion plasma from patients who develop TRALI. Blocking platelet activation reduces the production of NETs and lung injury, and inhibiting NETs by blocking extracellular histones or dismantling the NET structure with DNase1 are strongly protective in TRALI. In conclusion, TRALI is an immune-mediated event in which activated platelets, neutrophils, and NETs, contribute to injury and are therefore targets for therapeutic intervention.