Anti-HNA-3a induced TRALI and the effect of filtration on TRALI. (A) Anti-HNA-3a induced TRALI. Antibodies to HNA-3a are postulated to bind to primed neutrophils expressing HNA-3a, leading to activation, agglutination, and subsequent pulmonary injury resulting in TRALI. First, anti-HNA-3a in the blood component binds to human neutrophils expressing HNA-3a/CTL2-P1. Next, antibody-antigen interactions lead to agglutination of neutrophils and activation of the PMN oxidase. Then activated PMNs release ROS and enzymes that mediate endothelial damage, vascular compromise, and edema, subsequently leading to TRALI. NETs are postulated to form as a pathological bioproduct of neutrophil activation, leading to further endothelial injury. (B) Effect of filtration on TRALI. Modified and experimental Pall BPF4 leukoreduction filters deplete blood products of anti-HNA-3a among other antibodies. Reduction of TRALI-inducing substances in the blood component can result in decreased subsequent lung injury, as a potential preventative mechanism.