Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses.

Autor: Jongen MSA; Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK., MacArthur BD; Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.; Mathematical Sciences, University of Southampton, Southampton, SO17 1BJ, UK.; Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK., Englyst NA; Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.; Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK., West J; Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK. J.J.West@soton.ac.uk.; Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. J.J.West@soton.ac.uk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Jun 04; Vol. 3 (1), pp. 281. Date of Electronic Publication: 2020 Jun 04.
DOI: 10.1038/s42003-020-1002-5
Abstrakt: Investigations into the nature of platelet functional variety and consequences for homeostasis require new methods for resolving single platelet phenotypes. Here we combine droplet microfluidics with flow cytometry for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin > TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level responses in health and disease.
Databáze: MEDLINE
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