How different animal models help us understand TRALI

Transfusion-related acute lung injury (TRALI) is still one of the leading causes of transfusion-associated mortality, despite increased awareness and the implementation of various mitigation strategies. TRALI may be either antibody or nonantibody mediated. Understanding the underlying mechanism through clinical cases has been challenging because of the low and unpredictable incidence. Thus, animal models provide an important tool for investigating the mechanism of TRALI in a controlled and systematic fashion. One of the earliest animal models, an ex vivo rabbit lung model, revealed the role of anti-5b (anti-HNA-3a) and granulocytes. In vivo models with mice, rats and pig models have provided further insights into the mechanisms of antibody-mediated TRALI. There is evidence for contributions from neutrophils, neutrophil extracellular traps, platelets, lymphocytes, monocytes and endothelial cells. Elevated levels of C-reactive proteins and cardiopulmonary bypass may predispose to TRALI, while protective roles have been identified with lymphocytes, T-regulatory cells and dendritic cells. Mouse models have shown that IL-10 infusion protects from TRALI if administered prophylactically and successfully treats TRALI reaction if administered therapeutically. Silliman et al. introduced the non-immune mechanism of TRALI with rat models, and since then, there have been sheep and pig models. Nonimmune animal models have demonstrated the importance of a priming event (e.g. endotoxin administration) and a role for the protein and lipid biological response modifiers (BRMs) that accumulate during routine blood product storage. This paper focuses on how the key ex vivo and in vivo animal models have progressed our understanding of the mechanisms leading to TRALI