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- Title
Platelet-derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions.
- Authors
Marcoux, Genevieve; Magron, Audrey; Sut, Caroline; Laroche, Audree; Laradi, Sandrine; Hamzeh‐Cognasse, Hind; Allaeys, Isabelle; Cabon, Ophelie; Julien, Anne‐Sophie; Garraud, Olivier; Cognasse, Fabrice; Boilard, Eric; Hamzeh-Cognasse, Hind; Julien, Anne-Sophie
- Abstract
<bold>Background: </bold>Whereas platelet transfusion is a common medical procedure, inflammation still occurs in a fraction of transfused individuals despite the absence of any apparent infectious agents. Platelets can shed membrane vesicles, called extracellular vesicles (EVs), some of which contain mitochondria (mito+EV). With its content of damage-associated molecular pattern (DAMP), the mitochondrion can stimulate the innate immune system. Mitochondrial DNA (mtDNA) is a recognized DAMP detected in the extracellular milieu in numerous inflammatory conditions and in platelet concentrates. We hypothesized that platelet-derived mitochondria encapsulated in EVs may represent a reservoir of mtDNA.<bold>Study Design and Methods: </bold>Herein, we explored the implication of mito+EVs in the occurrence of mtDNA quantified in platelet concentrate supernatants that induced or did not induce transfusion adverse reactions.<bold>Results: </bold>We observed that EVs were abundant in platelet concentrates, and platelet-derived mito+EVs were more abundant in platelet concentrates that induced adverse reactions. A significant correlation (rs = 0.73; p < 0.0001) between platelet-derived mito+EV levels and mtDNA concentrations was found. However, there was a nonsignificant correlation between the levels of EVs without mitochondria and mtDNA concentrations (rs = -0.11; p = 0.5112). The majority of the mtDNA was encapsulated into EVs.<bold>Conclusion: </bold>This study suggests that platelet-derived EVs, such as those that convey mitochondrial DAMPs, may be a useful biomarker for the prediction of potential risk of adverse transfusion reactions. Moreover, our work implies that investigations are necessary to determine whether there is a causal pathogenic role of mitochondrial DAMP encapsulated in EVs as opposed to mtDNA in solution.
- Subjects
MITOCHONDRIAL DNA; BLOOD platelet transfusion; MITOCHONDRIA
- Publication
Transfusion, 2019, Vol 59, Issue 7, p2403
- ISSN
0041-1132
- Publication type
journal article
- DOI
10.1111/trf.15300