Biochemistry of storage lesions of red cell and platelet concentrates: A continuous fight implying oxidative/nitrosative/phosphorylative stress and signaling

Rinalducci, Sara; Zolla, Lello

doi:10.1016/j.transci.2015.04.005

Cited by 16 publications

(11 citation statements)

References 98 publications

(108 reference statements)

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“…The recommended shelf life of PCs, ranging from 3 to 7 days, is still a matter of discernment amongst different countries, where transfusion policies differ due to both the risk of bacterial contamination and the acknowledged platelet storage lesion (PSL) [48,49]. PSL is associated with reduced in vivo platelet recovery, survival and haemostatic activity after transfusion [50]. To identify protein changes due to storage, the proteome of freshly isolated platelets was compared with the proteome of platelets from PCs at storage days 1, 2, 6 and 8 ( Figure 2 and Table S3).…”

Section: Comparison Of the Proteome Of Fresh Platelets And Control Pcmentioning

confidence: 99%

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology

et al. 2018

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Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20-24°C) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens such as bacteria, viruses, and parasites. In this context, PITs, such as Mirasol Pathogen Reduction Technology (PRT), have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation, and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, that is, Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 1, 2, 6, and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. Data are available via ProteomeXchange with identifier PXD008119. We identified marginal differences between Mirasol PRT and Control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT. In addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to Mirasol PRT or PSL, and proves to be a methodology suitable to phenotype platelets in an unbiased manner, in various physiological contexts.

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Section: Comparison Of the Proteome Of Fresh Platelets And Control Pcmentioning

confidence: 99%

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology

et al. 2018

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“…During storage, changes in platelet metabolism occur 7 . Also an increase in levels of reactive oxygen species leading to oxidative stress has been reported 8 . Despite these findings, triggers for initiating the development of the PLS are still not fully elucidated.…”

Section: Introductionmentioning

confidence: 97%

Monitoring storage induced changes in the platelet proteome employing label free quantitative mass spectrometry

Rijkers

Eshof

Meer

et al. 2017

Sci Rep

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Shelf life of platelet concentrates is limited to 5–7 days due to loss of platelet function during storage, commonly referred to as the platelet storage lesion (PSL). To get more insight into the development of the PSL, we used label free quantitative mass spectrometry to identify changes in the platelet proteome during storage. In total 2501 proteins were accurately quantified in 3 biological replicates on at least 1 of the 7 different time-points analyzed. Significant changes in levels of 21 proteins were observed over time. Gene ontology enrichment analysis of these proteins revealed that the majority of this set was involved in platelet degranulation, secretion and regulated exocytosis. Twelve of these proteins have been shown to reside in α-granules. Upon prolonged storage (13–16 days) elevated levels of α-2-macroglobulin, glycogenin and Ig μ chain C region were identified. Taken together this study identifies novel markers for monitoring of the PSL that may potentially also be used for the detection of “young” and “old” platelets in the circulation.

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“…Deleterious changes to morphological, metabolic and haemostatic characteristics occurs during storage: a shift from typical resting state phenotype towards one of activation and apoptosis and or necrosis [[3], [4], [5]]. Declining mitochondrial function is central to the PSL with loss of mitochondrial membrane potential (Δψ m ), cytochrome c release, caspase activation and increased ROS production occurring [6,7]. In particular, intracellular superoxide production further promotes the PSL, encouraging platelet degranulation, cytokine release and oxidative damage of key proteins and membranes [5,8,9].…”

Section: Introductionmentioning

confidence: 99%

Acute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation

et al. 2019

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Background Bilirubin, a by-product of haem catabolism, possesses potent endogenous antioxidant and platelet inhibitory properties. These properties may be useful in inhibiting inappropriate platelet activation and ROS production; for example, during storage for transfusion. Given the hydrophobicity of unconjugated bilirubin (UCB), we investigated the acute platelet inhibitory and ROS scavenging ability of a water-soluble bilirubin analogue, bilirubin ditaurate (BRT) on ex vivo platelet function to ascertain its potential suitability for inclusion during platelet storage. Methods The inhibitory potential of BRT (10–100 μM) was assessed using agonist induced platelet aggregation, dense granule exocytosis and flow cytometric analysis of P-selectin and GPIIb/IIIa expression. ROS production was investigated by analysis of H 2 DCFDA fluorescence following agonist simulation while mitochondrial ROS production investigated using MitoSOX™ Red. Platelet mitochondrial membrane potential and viability was assessed using TMRE and Zombie Green™ respectively. Results Our data shows ≤35 μM BRT significantly inhibits both dense and alpha granule exocytosis as measured by ATP release and P-selectin surface expression, respectively. Significant inhibition of GPIIb/IIIa expression was also reported upon ≤35 μM BRT exposure. Furthermore, platelet exposure to ≤10 μM BRT significantly reduces platelet mitochondrial ROS production. Despite the inhibitory effect of BRT, platelet viability, mitochondrial membrane potential and agonist induced aggregation were not perturbed. Conclusions These data indicate, for the first time, that BRT, a water-soluble bilirubin analogue, inhibits platelet activation and reduces platelet ROS production ex vivo and may, therefore, may be of use in preserving platelet function during storage.

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Biochemistry of storage lesions of red cell and platelet concentrates: A continuous fight implying oxidative/nitrosative/phosphorylative stress and signaling

Cited by 16 publications

References 98 publications

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology

Monitoring storage induced changes in the platelet proteome employing label free quantitative mass spectrometry

Acute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation

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