Abstract: Objective To explore the feasibility and risks of using extracellular vesicles (EVs) secreted by tolerant dendritic cells (DC) to intervene in transfusion-related acute lung injury (TRALI). Methods Mouse bone marrow-derived DC cells were induced in vitro to become tolerant DCs by treatment with rapamycin, and the culture supernatant was collected and EVs were harvested by gradient centrifugation. Balb/c mice were induced into a TRALI disease model using LPS and anti-H2Kd antibodies, and EVs secreted by isogenic rapamycin-DCs or allogenic rapamycin-DCs were used to intervene in TRALI mice, and a series of data of diseased mice were observed and recorded. Results Compared with the TRALI onset group, after using rapamycin-treated tolerant DCs to intervene in TRALI onset mice, the mortality rate of the mice was significantly reduced. Unexpectedly, intervention with EVs generated from allogeneic tolerant DC (after rapamycin treatment) aggravated the mortality of TRALI. Despite EVs intervention, lung wet-to-dry ratio, pleural effusion and body temperature were not significantly different from those in mice treated with LPS and H2Kd antibodies alone. However, the mortality rate after EVs intervention was positively correlated with the injection concentration, even though the allogeneic vesicles were derived from tolerant cells and did not induce TRALI in mice when combined with LPS. Conclusion Allogeneic extracellular vesicle infusion combined with anti-leukocyte antibodies will increase the risk of death in TRALI, even though autologous DC has a protective effect on TRALI. Also, the allogeneic extracellular vesicles only combined with LPS does not cause respiratory distress. The data from this study suggest that we need to pay more attention on the risk of TRALI aggravated by the application of allogeneic EV therapies.

Key words: Transfusion-related acute lung injury, TRALI model, Dendritic cells, Extracellular vesicles