University of Utah Molecular Medicine Program.
Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
Curr Opin Hematol. 2021 Sep 1;28(5):301-307. doi: 10.1097/MOH.0000000000000665.
In this review, we will describe how the combined ability of platelets and neutrophils to interact with each other drives ischemic stroke brain injury.
Neutrophils are one of the first cells to respond during ischemic stroke. Although animals stroke models have indicated targeting neutrophils improves outcomes, clinical trials have failed to yield successful strategies. Platelets play a critical role in recruiting neutrophils to sites of injury by acting as a bridge to the injured endothelium. After initial platelet adhesion, neutrophils can rapidly bind platelets through P-selectin and glycoprotein Ibα. In addition, recent data implicated platelet phosphatidylserine as a novel key regulator of platelet-neutrophil interactions in the setting of ischemic stroke. Inhibition of procoagulant platelets decreases circulating platelet-neutrophil aggregates and thereby reduces infarct size. Platelet binding alters neutrophil function, which contributes to the injury associated with ischemic stroke. This includes inducing the release of neutrophil extracellular traps, which are neurotoxic and pro-thrombotic, leading to impaired stroke outcomes.
Platelet-neutrophil interactions significantly contribute to the pathophysiology of ischemic stroke brain injury. Better understanding the mechanisms behind their formation and the downstream consequences of their interactions will lead to improved therapies for stroke patients.
在这篇综述中，我们将描述血小板和中性粒细胞相互作用的综合能力如何导致缺血性脑卒中脑损伤。
中性粒细胞是缺血性脑卒中发生时最早响应的细胞之一。虽然动物脑卒中模型表明靶向中性粒细胞可以改善预后，但临床试验未能产生成功的策略。血小板通过充当与损伤内皮的桥梁，在招募中性粒细胞到损伤部位方面发挥关键作用。在最初的血小板黏附之后，中性粒细胞可以通过 P-选择素和糖蛋白 Ibα 快速结合血小板。此外，最近的数据表明，血小板磷脂酰丝氨酸是缺血性脑卒中环境中血小板-中性粒细胞相互作用的新型关键调节因子。抑制促凝血小板可减少循环血小板-中性粒细胞聚集，从而减少梗死面积。血小板结合改变中性粒细胞的功能，导致与缺血性脑卒中相关的损伤。这包括诱导中性粒细胞胞外诱捕网的释放，其具有神经毒性和促血栓形成作用，导致脑卒中结局受损。
血小板-中性粒细胞相互作用显著促进缺血性脑卒中脑损伤的病理生理学。更好地了解其形成的机制及其相互作用的下游后果，将为脑卒中患者带来更好的治疗方法。
