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Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Örebro University, School of Medical Sciences. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-1920-3962
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 1441Article in journal (Refereed) Published
Abstract [en]

It is recognised that platelets respond differently to activation, where a subpopulation of platelets adopt a procoagulant phenotype while others are aggregatory. However, it has not been thoroughly tested whether these subpopulations will remain in maximally activated samples, or if they are merely a result of different platelet sensitivities to agonist activation. Here platelets were activated with gradually increasing concentrations of thrombin and/or the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Platelet activation was investigated using a novel six-colour flow cytometry protocol evaluating exposure of phosphatidylserine, active conformation of the fibrinogen receptor αIIbβ3, α-granule and lysosomal release (P-selectin and LAMP-1 exposure), mitochondrial membrane integrity and platelet fragmentation. Upon activation by CRP-XL or thrombin+CRP-XL, platelets formed three differently sized subpopulations. Normal-sized platelets showed high exposure of aggregatory active αIIbβ3 and intact mitochondria, while the smaller platelets and platelet fragments showed high exposure of procoagulant phosphatidylserine. The distribution of platelets between the differently sized subpopulations remained stable despite high agonist concentrations. All three were still present after 30 and 60 min of activation, showing that all platelets will not have the same characteristics even after maximal stimulation. This suggests that platelet subpopulations with distinct activation patterns exist within the total platelet population.

Place, publisher, year, edition, pages
London, UK: Nature Publishing Group, 2018. Vol. 8, no 1, article id 1441
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-64716DOI: 10.1038/s41598-017-19126-8ISI: 000423045400014PubMedID: 29362366Scopus ID: 2-s2.0-85041015411OAI: oai:DiVA.org:oru-64716DiVA, id: diva2:1179486
Note

Funding Agency:

LiU Fund of U and Linköping University

Available from: 2018-02-01 Created: 2018-02-01 Last updated: 2018-02-06Bibliographically approved

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