Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation

Abstract Human platelet transformation into balloons is part of the haemostatic response and thrombus architecture. Here we reveal that in aggregates of platelets in plasma, ballooning in multiple platelets occurs in a synchronised manner. This suggests a mechanism of coordination between cells, pre...

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Autores principales: Ejaife O. Agbani, Christopher M. Williams, Ingeborg Hers, Alastair W. Poole
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/687bb9ef88c64ed9a873232060e73ace
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spelling oai:doaj.org-article:687bb9ef88c64ed9a873232060e73ace2021-12-02T16:06:33ZMembrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation10.1038/s41598-017-02933-42045-2322https://doaj.org/article/687bb9ef88c64ed9a873232060e73ace2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02933-4https://doaj.org/toc/2045-2322Abstract Human platelet transformation into balloons is part of the haemostatic response and thrombus architecture. Here we reveal that in aggregates of platelets in plasma, ballooning in multiple platelets occurs in a synchronised manner. This suggests a mechanism of coordination between cells, previously unrecognised. We aimed to understand this mechanism, and how it may contribute to thrombus development. Using spinning-disc confocal microscopy we visualised membrane ballooning in human platelet aggregates adherent to collagen-coated surfaces. Within an aggregate, multiple platelets undergo ballooning in a synchronised fashion, dependent upon extracellular calcium, in a manner that followed peak cytosolic calcium levels in the aggregate. Synchrony was observed in platelets within but not between aggregates, suggesting a level of intra-thrombus communication. Blocking phosphatidylserine, inhibiting thrombin or blocking PAR1 receptor, largely prevented synchrony without blocking ballooning itself. In contrast, inhibition of connexins, P2Y12, P2Y1 or thromboxane formation had no effect on synchrony or ballooning. Importantly, synchronised ballooning was closely followed by a surge in microvesicle formation, which was absent when synchrony was blocked. Our data demonstrate that the mechanism underlying synchronised membrane ballooning requires thrombin generation acting effectively in a positive feedback loop, mediating a subsequent surge in procoagulant activity and microvesicle release.Ejaife O. AgbaniChristopher M. WilliamsIngeborg HersAlastair W. PooleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ejaife O. Agbani
Christopher M. Williams
Ingeborg Hers
Alastair W. Poole
Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
description Abstract Human platelet transformation into balloons is part of the haemostatic response and thrombus architecture. Here we reveal that in aggregates of platelets in plasma, ballooning in multiple platelets occurs in a synchronised manner. This suggests a mechanism of coordination between cells, previously unrecognised. We aimed to understand this mechanism, and how it may contribute to thrombus development. Using spinning-disc confocal microscopy we visualised membrane ballooning in human platelet aggregates adherent to collagen-coated surfaces. Within an aggregate, multiple platelets undergo ballooning in a synchronised fashion, dependent upon extracellular calcium, in a manner that followed peak cytosolic calcium levels in the aggregate. Synchrony was observed in platelets within but not between aggregates, suggesting a level of intra-thrombus communication. Blocking phosphatidylserine, inhibiting thrombin or blocking PAR1 receptor, largely prevented synchrony without blocking ballooning itself. In contrast, inhibition of connexins, P2Y12, P2Y1 or thromboxane formation had no effect on synchrony or ballooning. Importantly, synchronised ballooning was closely followed by a surge in microvesicle formation, which was absent when synchrony was blocked. Our data demonstrate that the mechanism underlying synchronised membrane ballooning requires thrombin generation acting effectively in a positive feedback loop, mediating a subsequent surge in procoagulant activity and microvesicle release.
format article
author Ejaife O. Agbani
Christopher M. Williams
Ingeborg Hers
Alastair W. Poole
author_facet Ejaife O. Agbani
Christopher M. Williams
Ingeborg Hers
Alastair W. Poole
author_sort Ejaife O. Agbani
title Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
title_short Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
title_full Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
title_fullStr Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
title_full_unstemmed Membrane Ballooning in Aggregated Platelets is Synchronised and Mediates a Surge in Microvesiculation
title_sort membrane ballooning in aggregated platelets is synchronised and mediates a surge in microvesiculation
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/687bb9ef88c64ed9a873232060e73ace
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AT ingeborghers membraneballooninginaggregatedplateletsissynchronisedandmediatesasurgeinmicrovesiculation
AT alastairwpoole membraneballooninginaggregatedplateletsissynchronisedandmediatesasurgeinmicrovesiculation
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