Mitochondrial damage-associated molecular patterns as potential proinflammatory mediators in post-platelet transfusion adverse effects

BACKGROUND Platelet concentrates (PCs) are the most common blood components eliciting nonhemolytic transfusion reactions (NHTRs), such as allergic transfusion reactions and febrile reactions. However, the precise mechanisms of NHTRs in PC transfusion remain largely unknown. Previous studies reported...

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Bibliographic Details
Published in:Transfusion (Philadelphia, Pa.) Pa.), 2016-05, Vol.56 (5), p.1201-1212
Main Authors: Yasui, Kazuta, Matsuyama, Nobuki, Kuroishi, Ayumu, Tani, Yoshihiko, Furuta, Rika A., Hirayama, Fumiya
Format: Article
Language:English
Subjects:
Basophils - immunology
Blood
Blood Platelets - ultrastructure
Blood Safety
DNA, Mitochondrial - analysis
DNA, Mitochondrial - genetics
Humans
Immune System Phenomena
Inflammation Mediators
Japan
Mitochondria
Mitochondria - genetics
Mitochondrial DNA
Monocytes - immunology
Neutrophils
Neutrophils - immunology
Platelet Transfusion - adverse effects
Transfusion Reaction - etiology
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Summary:BACKGROUND Platelet concentrates (PCs) are the most common blood components eliciting nonhemolytic transfusion reactions (NHTRs), such as allergic transfusion reactions and febrile reactions. However, the precise mechanisms of NHTRs in PC transfusion remain largely unknown. Previous studies reported that mitochondria‐derived damage‐associated molecular patterns (DAMPs) could be important mediators of innate cell inflammation. Platelets (PLTs) represent a major reservoir of mitochondria in the blood circulation. The aim of this study was to determine the possible involvement of mitochondrial DAMPs in NHTRs. STUDY DESIGN AND METHODS The amount of mitochondrial DAMPs was determined as an index of total copy numbers of mitochondrial DNA (mtDNA), including mtDNA itself and free mitochondria, using quantitative real‐time polymerase chain reaction. To examine whether neutrophils, monocytes, and basophils were activated by mitochondrial DAMPs in vitro, an in vitro whole blood cell culture assay was performed. RESULTS In blood components associated with NHTRs, the mean total mtDNA concentration was highest in PCs followed in order by fresh‐frozen plasma and red blood cells. The amount of mtDNA in NHTR PCs was higher than that in control PCs without NHTRs. The mitochondrial DAMPs present in NHTR PCs was high enough to activate neutrophils, monocytes, and basophils, when costimulated with N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine or HLA antibodies. CONCLUSION PLT‐derived mitochondrial DAMPs are candidate risk factors for the onset of NHTRs.
ISSN:0041-1132
1537-2995
DOI:10.1111/trf.13535