ArticleBlood2021
Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 78 citations in OpenAlex.
- Aged versus fresh autologous platelet transfusion in a two-hit healthy volunteer model of transfusion-related acute lung injury.Transfusion · 2022Trial
- Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021).Annals of the American Thoracic Society · 2022Trial
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- In Vitro Modeling of Age-Associated Lipid Mediator's Impact on Vascular Biology Following Platelet Concentrate Transfusion.Aging cell · 2026Article
- From platelets to particles: Optimizing extracellular vesicle isolation in a National Blood Centre.Vox sanguinis · 2026Article
- Comparative phenotyping of surface markers and glycans in murine and human platelet-derived extracellular vesicles.Research and practice in thrombosis and haemostasis · 2026Article
- Mouse Models of Transfusion-Related Acute Lung Injury (TRALI).Methods in molecular biology (Clifton, N.J.) · 2026Article
- Pre-storage leucoreduction of platelet concentrates reduced biological response modifier concentrations and TRALI incidence in an in vivo sheep model.Scientific reports · 2025Article
- Extracellular vesicles in cancer´s communication: messages we can read and how to answer.Molecular cancer · 2025Review
- Transfusion-Related Acute Lung Injury: from Mechanistic Insights to Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Deciphering Platelets: Are They Cells or an Evolved Form of Extracellular Vesicles?Circulation research · 2025Review
- From Plant Based Therapy to Plant-Derived Vesicle-Like Nanoparticles for Cancer Treatment: Past, Present and Future.International journal of nanomedicine · 2025Review
- Recent developments in microfluidic passive separation to enable purification of platelets for transfusion.Biomicrofluidics · 2024Review
- Monitoring Cell Activation and Extracellular Vesicle Generation in Platelet Concentrates for Transfusion.International journal of molecular sciences · 2024Article
- Ten things ICU specialists need to know about platelet transfusions.Intensive care medicine · 2024Article
- Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing.Journal of nanobiotechnology · 2024Review
- Preservation of recipient plasma sphingosine-1-phosphate levels reduces transfusion-related acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Separation of platelets by size in a microfluidic device based on controlled incremental filtration.Lab on a chip · 2024Article
- Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.Nature cardiovascular research · 2023Article
- Different Expression Profiles of Exosomal circRNAs from Apheresis Platelets during Storage.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023Article
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Authors and funding
12 authors at 3 institutions in 4 countries.
Funding
Abstract
Transfusion-related acute lung injury (TRALI) is a hazardous transfusion complication with an associated mortality of 5% to 15%. We previously showed that stored (5 days) but not fresh platelets (1 day) cause TRALI via ceramide-mediated endothelial barrier dysfunction. As biological ceramides are hydrophobic, extracellular vesicles (EVs) may be required to shuttle these sphingolipids from platelets to endothelial cells. Adding to complexity, EV formation in turn requires ceramide. We hypothesized that ceramide-dependent EV formation from stored platelets and EV-dependent sphingolipid shuttling induces TRALI. EVs formed during storage of murine platelets were enumerated, characterized for sphingolipids, and applied in a murine TRALI model in vivo and for endothelial barrier assessment in vitro. Five-day EVs were more abundant, had higher long-chain ceramide (C16:0, C18:0, C20:0), and lower sphingosine-1-phosphate (S1P) content than 1-day EVs. Transfusion of 5-day, but not 1-day, EVs induced characteristic signs of lung injury in vivo and endothelial barrier disruption in vitro. Inhibition or supplementation of ceramide-forming sphingomyelinase reduced or enhanced the formation of EVs, respectively, but did not alter the injuriousness per individual EV. Barrier failure was attenuated when EVs were abundant in or supplemented with S1P. Stored human platelet 4-day EVs were more numerous compared with 2-day EVs, contained more long-chain ceramide and less S1P, and caused more endothelial cell barrier leak. Hence, platelet-derived EVs become more numerous and more injurious (more long-chain ceramide, less S1P) during storage. Blockade of sphingomyelinase, EV elimination, or supplementation of S1P during platelet storage may present promising strategies for TRALI prevention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.