Effects of Mirasol PRT treatment on storage lesion development in plasma‐stored apheresis‐derived platelets compared to untreated and irradiated units

Picker, Susanne M.; Steisel, Alexander; Gathof, Birgit

doi:10.1111/j.1537-2995.2008.01778.x

Cited by 61 publications

(108 citation statements)

References 38 publications

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“…As compared to untreated C units, the lower annexin V release of M units combined with higher HSRs, at least until storage day 5, could have resulted from differences in glucose metabolism, leading to better energy maintenance after PRT treatment with riboflavin-UVB. As reported previously, compared to untreated PLTs, riboflavin-UVB-treated PLTs exhibited an obviously up-regulated mitochondria-based respiration [25], which delivers profoundly more ATP than the anaerobic glycolytic pathway. On the other hand, PRT treatment with the psoralen-based technology appeared to impair oxidative phosphorylation [26].…”

Section: Discussionsupporting

confidence: 48%

“…Evaluation of PLT count, contamination with red and white blood cells via flow cytometry, LDH release, HSR, and bacterial contamination with the Bactec ® culturing system (Becton Dickinson, San Jose, CA, USA) were performed as described previously [25,26]. The pH value was analyzed at 37 °C on an automated blood gas analyzer (Rapidlab 1260, Siemens Medical Solutions Diagnostics mbH, Fernwald, Germany) and corrected to 22 °C.…”

Section: Analysis Of Cell Count Ldh Release Ph Hypotonic Shock Resmentioning

confidence: 99%

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Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Picker

Oustianskaia

Schneider

et al. 2010

Transfus Med Hemother

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Background: In vitro function of stored platelet (PLT) con-centrates was analyzed after applying two different techniques of pathogen reduction technology (PRT) treatment, which could increase cellular injury during processing and storage. Methods: Nine triple-dose PLT apheresis donations were split into 27 single units designated to riboflavin-UVB (M) or psoralen-UVA (I) treatment or remained untreated (C). Throughout 8 days of storage, samples were analyzed for annexin V release, the mitochondrial transmembrane potential (ΔΨ) and some classical markers of PLT quality (pH, LDH release, hypotonic shock response (HSR)). Results: PLT count and LDH release of all units maintained initial ranges. All units exhibited a decrease in pH and HSR and an increase in annexin V release and ΔΨ disruption. Notably, throughout the entire storage period, annexin V release re-mained lowest in M units. Throughout 7 days of storage, M units remained comparable to C units (p > 0.05), whereas inferior values were observed with I units. Here, differences to C units reached significance by day 1 (pH: p < 0.0001), day 5 (annexin V release: p < 0.014), and day 7 (HSR, ΔΨ: p ≤ 0.003). After PRT treatment, annexin V release and ΔΨ disruption were significantly (p < 0.001) correlated with pH and HSR. Conclusion: During storage, all units showed a de-crease in HSR and an increase in acidity, annexin V release and ΔΨ disruption. While M units remained comparable to C units, I units demonstrated significantly inferior values dur-ing terminal storage. This could have resulted from differences in PRT treatment or simply be due to differences in storage media and should be analyzed for clinical relevance in future investigations.

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Section: Discussionsupporting

confidence: 48%

Section: Analysis Of Cell Count Ldh Release Ph Hypotonic Shock Resmentioning

confidence: 99%

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Picker

Oustianskaia

Schneider

et al. 2010

Transfus Med Hemother

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“…[8][9][10] Mitochondrial membrane depolarization occurs in PCs during blood bank storage and further increases upon PI treatment. [11][12][13] Recently, we and other groups have demonstrated that apoptotic events including phosphatidylserine (PS) exposure, increased proapoptotic protein expression, and caspase activation are triggered by RF/UV treatment in stored PCs, further supporting the model that apoptosis is involved in development of the PLT storage lesion. 14,15 However, the detailed biochemical mechanism(s) triggered by RF/UV are still unclear.…”

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confidence: 84%

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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“…A number of studies have concluded that Mirasol treatment exacerbates the effects of the platelet storage lesion, resulting in increased glucose consumption, lactate production, and increased markers of platelet activation [2,3,4,5,6]. Further, we and others have previously demonstrated that Mirasol treatment affects platelet signal transduction and apoptotic protein expression [7,8,9,10].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation

Johnson¹,

Marks²

2015

Transfus Med Hemother

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Background: Pathogen inactivation (PI) technologies for platelets aim to improve transfusion safety by preventing the replication of contaminating pathogens. However, as a consequence of treatment, aspects of the platelet storage lesion are amplified. Mirasol treatment also affects platelet signal transduction and apoptotic protein expression. The aim of this study was to examine the effect of Mirasol treatment on the generation of reactive oxygen species (ROS) and subsequent oxidative stress. Methods: Pooled platelet concentrates were prepared in platelet-additive solution (70% SSP+ / 30% plasma). ABO-matched platelets were pooled and split, and treated with the Mirasol system (TerumoBCT) or left untreated as a control. Platelet samples were tested on day 1, 5, and 7 post-collection. Results: Mirasol-treated platelets had increased formation of ROS by day 5 of storage. Oxidative damage, in the form of protein carbonylation, was higher in Mirasol-treated platelets, whilst no effect on nitrotyrosine formation or lipid peroxidation was detected. The NF-κB signaling pathway was also activated in Mirasol-treated platelets, with increased expression and phosphorylation of NF-κB p65 and IκBa. Conclusion: These data demonstrate that Mirasol-treated platelets produce more ROS and display protein alterations consistent with oxidative damage.

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Effects of Mirasol PRT treatment on storage lesion development in plasma‐stored apheresis‐derived platelets compared to untreated and irradiated units

Abstract: Although storage variables clearly showed the effects of PRT treatment, apheresis PLTs treated with Mirasol PRT retained cell quality during 5 days of storage without loss of mitochondria-based oxidative respiration.

Cited by 61 publications

References 38 publications

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

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

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation

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Effects of Mirasol PRT treatment on storage lesion development in plasma‐stored apheresis‐derived platelets compared to untreated and irradiated units

Abstract: Although storage variables clearly showed the effects of PRT treatment, apheresis PLTs treated with Mirasol PRT retained cell quality during 5 days of storage without loss of mitochondria-based oxidative respiration.

Cited by 61 publications

References 38 publications

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

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

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-&#954;B Activation

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Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation