Platelet activation by charged ligands and nanoparticles: platelet glycoprotein receptors as pattern recognition receptors

Samantha J. Montague*, Pushpa Patel, Eleyna M. Martin, Alexandre Slater, Lourdes Garcia Quintanilla, Gina Perrella, Caroline Kardeby, Magdolna Nagy, Diego Mezzano, Paula M. Mendes, Steve P. Watson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Charge interactions play a critical role in the activation of the innate immune system by damage- and pathogen-associated molecular pattern receptors. The ability of these receptors to recognize a wide spectrum of ligands through a common mechanism is critical in host defense. In this article, we argue that platelet glycoprotein receptors that signal through conserved tyrosine-based motifs function as pattern recognition receptors (PRRs) for charged endogenous and exogenous ligands, including sulfated polysaccharides, charged proteins and nanoparticles. This is exemplified by GPVI, CLEC-2 and PEAR1 which are activated by a wide spectrum of endogenous and exogenous ligands, including diesel exhaust particles, sulfated polysaccharides and charged surfaces. We propose that this mechanism has evolved to drive rapid activation of platelets at sites of injury, but that under some conditions it can drive occlusive thrombosis, for example, when blood comes into contact with infectious agents or toxins. In this Opinion Article, we discuss mechanisms behind charge-mediated platelet activation and opportunities for designing nanoparticles and related agents such as dendrimers as novel antithrombotics.

Original languageEnglish
Pages (from-to)1018-1030
Number of pages13
JournalPlatelets
Volume32
Issue number8
Early online date18 Jul 2021
DOIs
Publication statusPublished - 17 Nov 2021

Keywords

  • CLEC-2
  • GPVI
  • nanoparticles
  • pattern recognition receptors
  • PEAR1
  • platelets
  • PLATINUM NANOPARTICLES
  • GOLD NANOPARTICLES
  • CARBON NANOTUBES
  • THROMBUS FORMATION
  • PROTEIN CORONA
  • HUMAN BLOOD
  • IN-VITRO
  • AGGREGATION
  • MECHANISMS

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