Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response, Dependent on Both Numbers and Storage Duration

BACKGROUND: Transfusion of red blood cells (RBCs) is associated with adverse outcome, but the causative factor is unknown. Extracellular vesicles (EVs) have pro-inflammatory properties. We hypothesized that EVs released from both fresh and stored RBC products can induce a host inflammatory response in a dose-dependent manner. METHODS: Whole blood was incubated with supernatant from RBC units stored for different time periods, either containing (different numbers of) EVs or depleted from EVs. RESULTS: Incubation with both fresh and stored supernatant containing EVs induced a strong host response with production of TNF, IL-6 and IL-8. In supernatant depleted from EVs, this host response was completely abrogated. IL-10 levels were not affected. EV-induced host response was both dependent on the number of EVs as well as on storage time. CONCLUSIONS: EVs from both fresh and stored RBC units illicit a strong inflammatory host response in recipients and may therefore contribute to adverse outcome of RBC transfusion.