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.
|Number of pages||13|
|Early online date||16 Jul 2021|
|Publication status||E-pub ahead of print - 16 Jul 2021|
Bibliographical note© 2021 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This research was funded, in whole or in part, by Wellcome Trust, Grant 204951/Z/16/Z]. A CC BY licence is applied to [the AAM/the VoR] arising from this submission, in accordance with the grant’s open access conditions. This work was also supported by the British Heart Foundation (BHF: CH03/003) and the European Research Council (ERC: Consolidator Grant 614787). S.J.M. is also supported by the BHF Accelerator Award (AA/18/2/34218). P.P. is supported by the
Engineering and Physical Sciences Research Coucil (EP/L015749/1). C. K. is supported by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Actions Individual Fellowship grant agreement [No 893262], project PAELLA. D.M. is supported by Fondecyt Project 1181681;Fondo Nacional de Desarrollo Científico y Tecnológico ;
- pattern recognition receptors