Platelet-derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions.


Journal

Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360

Informations de publication

Date de publication:
07 2019
Historique:
received: 09 01 2019
revised: 06 03 2019
accepted: 10 03 2019
pubmed: 12 4 2019
medline: 28 5 2020
entrez: 12 4 2019
Statut: ppublish

Résumé

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. 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. 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 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.

Sections du résumé

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
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.

Identifiants

pubmed: 30973972
doi: 10.1111/trf.15300
doi:

Substances chimiques

DNA, Mitochondrial 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2403-2414

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

© 2019 AABB.

Auteurs

Genevieve Marcoux (G)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.

Audrey Magron (A)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.

Caroline Sut (C)

Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France.
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France.

Audree Laroche (A)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.

Sandrine Laradi (S)

Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France.
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France.

Hind Hamzeh-Cognasse (H)

Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France.

Isabelle Allaeys (I)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.

Ophelie Cabon (O)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.

Anne-Sophie Julien (AS)

Department of Mathematics and Statistic, Université Laval, Quebec City, Québec, Canada.

Olivier Garraud (O)

Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France.

Fabrice Cognasse (F)

Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France.
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France.

Eric Boilard (E)

Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada.
Canadian National Transplantation Research Program, Edmonton, Alberta, Canada.

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Classifications MeSH