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Internalization of microparticles by platelets is partially mediated by toll-like receptor 4 and enhances platelet

Didac Jerez-Dolz1, Sergi Torramade-Moix1, Marta Palomo2

  • 1Hematopathology, Pathological Anatomy, Hospital Clinic of Barcelona, Biomedical Diagnosis Centre (CDB), Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Atherosclerosis
|January 17, 2020
PubMed
Abstract

Insights

Platelets internalize circulating platelet microparticles (PMP), increasing blood clot formation. This process involves toll-like receptor 4 (TLR-4) and can be inhibited by blocking TLR-4, suggesting a therapeutic target for thrombotic events.

Area of Science:

  • Hematology
  • Immunology
  • Cell Biology

Background:

  • Circulating platelet microparticles (PMP) are abundant, procoagulant, and interact with inflammatory cells.
  • Understanding PMP interactions with platelets is crucial for comprehending thrombotic and inflammatory processes.

Purpose of the Study:

  • To investigate the interaction between platelet microparticles (PMP) and platelets.
  • To explore the role of toll-like receptor 4 (TLR-4) in PMP-platelet interactions.

Main Methods:

  • PMP were isolated from expired platelet concentrates.
  • PMP were incubated with washed platelets, platelet-rich plasma, and whole blood.
  • Techniques included flow cytometry, electron microscopy, aggregometry, and thromboelastometry (ROTEM); anti-TLR-4 antibody was used to assess inhibition.

Main Results:

  • Platelets internalized PMP, confirmed by microscopy and flow cytometry.
  • PMP increased heterotypic aggregate formation, platelet aggregation, and accelerated clotting times.
  • Inhibition of TLR-4 reduced PMP-platelet association, prevented aggregate formation, and normalized clotting parameters.

Conclusions:

  • Platelets internalize their own PMP, enhancing thrombogenicity.
  • This internalization process is partly mediated by the innate immunity receptor TLR-4.
  • Targeting TLR-4 may offer a strategy to mitigate PMP-induced thrombotic events.
Keywords:
EndocytosisInnate immunityInternalizationPhagocytosisPlatelet microparticlesTLR-4Thrombogenicity

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