Grant: Operating Grant - PA: Transfusion Related Acute Lung Injury (TRALI)

Lung injury is the most frequent cause of mortality related to the transfusion of stored blood products. Transfusion-related acute lung injury (TRALI) can develop in two ways: Either through the presence of antibodies in the blood products which react with their respective antigens in the transfused patient, or through time-dependent alterations in blood products with longer storage times causing increasing degrees of lung injury. While recent research has unraveled important factors of antibody-mediated TRALI, the mechanisms of antibody-independent TRALI are still largely obscure. Here, we propose to bridge this critical knowledge gap by use of our newly established mouse model that allows for the first time an in depth interrogation of the pathomechanisms underlying antibody-independent TRALI. Based on preliminary data, we will focus specifically on two key mechanisms by which storage-time dependent changes in blood products may trigger TRALI: First, we will assess whether blood cell storage increases the formation of microparticles, small vesicles that can be released by cells and serve as intercellular communication shuttles with important roles in the propagation of injurious effects. Second, we will analyze the release of active biolipids from stored blood products and assess their functional role in the induction of TRALI. We expect the results of this work to provide important new mechanistic insights that translate into an extended safety of stored blood products. A better knowledge of the factors that limit storage time is also anticipated to increase the availability of blood products, which frequently remain a scarce clinical resource as of yet.