Platelet‐derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions
Abstract
BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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 (r s = 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 (r s = −0.11; p = 0.5112). The majority of the mtDNA was encapsulated into EVs. CONCLUSION: 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.
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- Authors
- Marcoux, G., Magron, A., Sut, C., Laroche, A., Laradi, S., Hamzeh‐Cognasse, H., Allaeys, I., Cabon, O., Julien, A., Garraud, O., Cognasse, F., & Boilard, E.
- Affiliations
- Department of Infectious Diseases and Immunity Centre de Recherche du CHU de Québec ‐ Université Laval Quebec City Québec Canada
- Centre de recherche du CHU de Québec-Université Laval (CA)
- Université de Lyon (FR)
- Université Laval (CA)
- Corresponding author
- Cognasse, Fabrice
- Venue
- Transfusion
- Publisher
- Wiley
- Published
- 2019-04-11
- Volume
- 59
- Issue
- 7
- Pages
- 2403-2414
- ISSN
- 0041-1132 (ISSN-L)
- 1537-2995
- OpenAlex
- W2938872713
- Cited by
- 87
- References
- 67
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 11 · 2023: 15 · 2022: 15 · 2021: 9 · 2020: 13 · 2019: 2
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Transfusion (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Canadian Blood Services
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- platelet-derived extracellular vesicles, mitochondrial DAMPs, mitochondrial DNA, platelet concentrates, transfusion reactions, innate immunity
- MeSH terms
- Extracellular Vesicles, Blood Platelets, DNA, Mitochondrial, Humans, Inflammation, Platelet Transfusion, Transfusion Reaction
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