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

Ejaife Agbani*, Chris Williams, Ingeborg Hers, Alastair Poole

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

21 Citations (Scopus)
283 Downloads (Pure)

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.
Original languageEnglish
Article number2770
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 5 Jun 2017

Bibliographical note

20-Apr-17

Keywords

  • Synchronised membrane ballooning
  • thrombin
  • microvesicles
  • phosphatidylserine exposure
  • aggregation
  • platelets
  • thrombosis

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