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Platelet extracellu...
Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat
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- McVey, Mark J. (författare)
- Saint Michael's Hospital,Hospital for Sick Children, Toronto,Ryerson University,University of Toronto
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- Weidenfeld, Sarah (författare)
- Charité - University Medicine Berlin
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- Maishan, Mazharul (författare)
- Saint Michael's Hospital
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- Spring, Chris (författare)
- Saint Michael's Hospital
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- Kim, Michael (författare)
- Saint Michael's Hospital
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- Tabuchi, Arata (författare)
- Saint Michael's Hospital
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- Srbely, Victoria (författare)
- Saint Michael's Hospital
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- Takabe-French, Alisa (författare)
- Saint Michael's Hospital
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- Simmons, Szandor (författare)
- Charité - University Medicine Berlin
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- Arenz, Christoph (författare)
- Humboldt University of Berlin
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- Semple, John W. (författare)
- Lund University,Lunds universitet,Trombocyt immunologi,Forskargrupper vid Lunds universitet,Platelet Immunology,Lund University Research Groups,University of Toronto,Saint Michael's Hospital
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- Kuebler, Wolfgang M. (författare)
- University of Toronto,Saint Michael's Hospital,Charité - University Medicine Berlin
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(creator_code:org_t)
- American Society of Hematology, 2021
- 2021
- Engelska 12 s.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:5, s. 690-701
- Relaterad länk:
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http://dx.doi.org/10...
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https://ashpublicati...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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. Key Points: • EVs derived from stored platelets cause TRALI as a function of their elevated ceramide and decreased S1P content. • Inhibiting ceramide formation, supplementing S1P, or washing stored platelets could potentially reduce TRALI incidence and severity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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McVey, Mark J.
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Weidenfeld, Sara ...
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Maishan, Mazharu ...
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Spring, Chris
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Kim, Michael
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Tabuchi, Arata
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visa fler...
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Srbely, Victoria
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Takabe-French, A ...
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Simmons, Szandor
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Arenz, Christoph
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Semple, John W.
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Kuebler, Wolfgan ...
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visa färre...
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