Ebeyer-Masotta Marie, Eichhorn Tanja, Weiss René, Lauková Lucia, Weber Viktoria
Center for Biomedical Technology, Department for Biomedical Research, University for Continuing Education Krems, Krems, Austria.
Front Cell Dev Biol. 2022 Jul 6;10:914891. doi: 10.3389/fcell.2022.914891. eCollection 2022.
Activated platelets and platelet-derived extracellular vesicles (EVs) have emerged as central players in thromboembolic complications associated with severe coronavirus disease 2019 (COVID-19). Platelets bridge hemostatic, inflammatory, and immune responses by their ability to sense pathogens via various pattern recognition receptors, and they respond to infection through a diverse repertoire of mechanisms. Dysregulated platelet activation, however, can lead to immunothrombosis, a simultaneous overactivation of blood coagulation and the innate immune response. Mediators released by activated platelets in response to infection, such as antimicrobial peptides, high mobility group box 1 protein, platelet factor 4 (PF4), and PF4 extracellular vesicles promote neutrophil activation, resulting in the release of neutrophil extracellular traps and histones. Many of the factors released during platelet and neutrophil activation are positively charged and interact with endogenous heparan sulfate or exogenously administered heparin via electrostatic interactions or via specific binding sites. Here, we review the current state of knowledge regarding the involvement of platelets and platelet-derived EVs in the pathogenesis of immunothrombosis, and we discuss the potential of extracorporeal therapies using adsorbents functionalized with heparin to deplete platelet-derived and neutrophil-derived mediators of immunothrombosis.
活化血小板和血小板衍生的细胞外囊泡（EVs）已成为与严重2019冠状病毒病（COVID-19）相关的血栓栓塞并发症的核心因素。血小板通过其经由各种模式识别受体感知病原体的能力，在止血、炎症和免疫反应之间架起桥梁，并且它们通过多种机制对感染作出反应。然而，血小板活化失调可导致免疫血栓形成，即血液凝固和先天免疫反应同时过度激活。活化血小板在感染时释放的介质，如抗菌肽、高迁移率族蛋白B1、血小板因子4（PF4）和PF4细胞外囊泡，可促进中性粒细胞活化，导致中性粒细胞胞外陷阱和组蛋白的释放。血小板和中性粒细胞活化过程中释放的许多因子带正电荷，并通过静电相互作用或通过特定结合位点与内源性硫酸乙酰肝素或外源性肝素相互作用。在此，我们综述了关于血小板和血小板衍生的EVs在免疫血栓形成发病机制中所起作用的当前知识状态，并讨论了使用肝素功能化吸附剂进行体外治疗以清除免疫血栓形成的血小板衍生和中性粒细胞衍生介质的潜力。
