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

Yasui, Kazuta; Matsuyama, Nobuki; Kuroishi, Ayumu; Tani, Yoshihiko; Furuta, Rie; Hirayama, Fumiya

doi:10.1111/trf.13535

Cited by 45 publications

(47 citation statements)

References 56 publications

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“…Our own group has reported that there is a direct relationship between (i) the secretion of sCD40L [proved to exert a pathogenic effect in certain recipients, together with companion BRMs Ox40L and IL-27 (64, 65)] and the component shelf life; and (ii) between the net amount of sCD40L (alongside potentiating molecules IL-13 or MIP-1α) and the manifestation of an inflammatory AE in the recipient (62). Similar findings exist for mitochondrial DNA (66–68). In addition, it has also been proposed that the techniques used to obtain PCs influence pro-inflammatory reactions, as these techniques do not expose platelets to the same stress (62, 69).…”

Section: Models Of Transfusion-associated Inflammation Hitsupporting

confidence: 81%

Transfusion as an Inflammation Hit: Knowns and Unknowns

et al. 2016

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Transfusion of blood cell components is frequent in the therapeutic arsenal; it is globally safe or even very safe. At present, residual clinical manifestations are principally inflammatory in nature. If some rare clinical hazards manifest as acute inflammation symptoms of various origin, most of them linked with conflicting and undesirable biological material accompanying the therapeutic component (infectious pathogen, pathogenic antibody, unwanted antigen, or allergen), the general feature is subtler and less visible, and essentially consists of alloimmunization or febrile non-hemolytic transfusion reaction. The present essay aims to present updates in hematology and immunology that help understand how, when, and why subclinical inflammation underlies alloimmunization and circumstances characteristic of red blood cells and – even more frequently – platelets that contribute inflammatory mediators. Modern transfusion medicine makes sustained efforts to limit such inflammatory hazards; efforts can be successful only if one has a clear view of each element’s role.

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Section: Models Of Transfusion-associated Inflammation Hitsupporting

confidence: 81%

Transfusion as an Inflammation Hit: Knowns and Unknowns

et al. 2016

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“…mtDNA is a highly potent inflammatory mediator when present extracellularly 26,43 and may cause transfusion-related side effects. 44 We observed that the level of extracellular mtDNA did not significantly increase in apheresis PCs upon the RF/UV treatment and during storage. Recently, Cognasse and coworkers 45 reported that extracellular mtDNA is consistently increased in PCs from Day 1 to Day 4 but decreased on Day 5 of storage.…”

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confidence: 67%

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

et al. 2017

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BACKGROUND: Biochemical analyses of mechanisms triggered in platelets (PLTs) upon pathogen inactivation (PI) are crucial to further understand the impact of PI on PLT functionality and, subsequently, quality. STUDY DESIGN AND METHODS: PLT concentrates(PCs) were split into four small illumination bags: 1) untreated control, 2) treated with riboflavin and ultraviolet light (RF/UV), and spiked with 3) solvent control dimethyl sulfoxide and 4) p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 before RF/UV treatment. Flow cytometry was used to monitor PLT mitochondrial potential (DW m ); generation of intracellular reactive oxygen species (ROS); and release of microvesicles (MVs), mitochondria (MT), and MVs containing MT (MVs/ MT). Quantitative polymerase chain reaction (qPCR) was used to quantify extracellular mitochondrial DNA (mtDNA). Translocation of selected mitochondrial proteins was analyzed in subcellular fractions by immunoblot.RESULTS: RF/UV treatment triggered an increased mitochondrial translocation of both Bax and Bid (p < 0.05, Day 7) and cytochrome c release (p < 0.01, Day 7), loss of DW m (p < 0.05, Day 5 and Day 7), and ROS generation (p < 0.01, Day 5 and Day 7) in PCs compared to the untreated control during storage. These PI-triggered changes were inhibited by SB203580 (p < 0.05). The release of MVs, MT, and MVs/MT was increased upon the RF/UV treatment during storage (p < 0.05) and, with the exception of MT, the release was decreased by the inhibitor (p < 0.05). qPCR analysis showed that RF/UV does not trigger mtDNA release during storage. CONCLUSION:These findings further our understanding of mechanisms in PLTs initiated by the RF/UV treatment, demonstrating that this treatment induces p38 MAPK-dependent mitochondrial signaling and MV release in apheresis PCs. R iboflavin and ultraviolet light (RF/UV) treatment is one of several pathogen inactivation (PI) technologies currently available.1 These treatments aim to target the replication and/or proliferation mechanism of pathogens and to destroy residual white blood cells (WBCs) to improve the safety of blood 14,15,25 The aim of this study was to evaluate the effects of RF/UV treatment on PLT mitochondrial function and signaling, including the recently discovered release of MT by PLTs, and to determine whether p38 is involved in the modulation of these mechanisms. MATERIALS AND METHODS MaterialsCommon chemicals were purchased from Sigma-Aldrich or Fisher Scientific. SB203580, a p38 MAPK inhibitor, was purchased from Santa Cruz Biotechnology. Apheresis PC preparationThis study was approved by the research ethics board of Canadian Blood Services and informed consent was obtained from all healthy volunteers before blood donation. Phlebotomy and plateletpheresis were carried out by the NetCAD development laboratory of Canadian Blood Services (Vancouver, Canada) using a Trima Accel (TerumoBCT). RF/UV treatment and inhibitor studyThe SB inhibitor stock solution in dimethyl sulfoxide (DMSO) was diluted in phosphate-buffered saline (PBS) and...

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“…We previously reported that the BAT was used as a functional test in transfusion medicine to assess the causal relationship between ATRs and the transfusion and to examine whether the reactions occurred through an allergen/IgE‐dependent or allergen/IgE‐independent pathway . Moreover, both pathways of basophil activation can be assessed by the BAT . However, those studies had several limitations.…”

Section: Discussionmentioning

confidence: 99%

Clinical utility of a passive immune basophil activation test for the analysis of allergic transfusion reactions

et al. 2017

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

Abstract: PLT-derived mitochondrial DAMPs are candidate risk factors for the onset of NHTRs.

Cited by 45 publications

References 56 publications

Transfusion as an Inflammation Hit: Knowns and Unknowns

Transfusion as an Inflammation Hit: Knowns and Unknowns

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

Clinical utility of a passive immune basophil activation test for the analysis of allergic transfusion reactions

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