Neutrophil extracellular traps (NETs) comprise decondensed chromatin, histones and neutrophil granular proteins and are involved in the response to infectious as well as non-infectious diseases. The prothrombotic activity of NETs has been reported in various thrombus-related diseases; this activity can be attributed to the fact that the NETs serve as a scaffold for cells and numerous coagulation factors and stimulate fibrin deposition. A crosstalk between NETs and thrombosis has been indicated to play a role in numerous thrombosis-related conditions including stroke. In cerebral ischemia, neutrophils are the first group of cells to infiltrate the damaged brain tissue, where they produce NETs in the brain parenchyma and within blood vessels, thereby aggravating inflammation. Increasing evidences suggest the connection between NETosis and thrombosis as a possible cause of “tPA resistance”, a problem encountered during the treatment of stroke patients. Several damage-associated molecular pattern molecules have been proven to induce NETosis and thrombosis, with high mobility group box 1 (HMGB1) playing a critical role. This review discusses NETosis and thrombosis and their crosstalk in various thrombosis-related diseases, focusing on the role of HMGB1 as a mediator in stroke. We also addresses the function of peptidylarginine deiminase 4 with respect to the interplay with HMGB1 in NET-induced thrombosis.

中文翻译：

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HMGB1在缺血性卒中NETosis和血栓形成之间的相互作用中的作用：综述。

中性粒细胞胞外诱捕器（NETs）包含缩合的染色质，组蛋白和中性粒细胞颗粒蛋白，并参与对传染性和非传染性疾病的反应。NETs在多种血栓相关疾病中都有促血栓形成的活性。这种活性可以归因于以下事实：NETs充当细胞和众多凝血因子的支架，并刺激纤维蛋白沉积。NET与血栓形成之间的串扰已被表明在许多与血栓形成相关的疾病（包括中风）中起作用。在脑缺血中，嗜中性白细胞是渗透到受损脑组织的第一组细胞，它们在脑实质和血管内产生NET，从而加剧炎症。越来越多的证据表明，NETosis和血栓形成之间的联系是“ tPA抵抗”的可能原因，这是中风患者治疗期间遇到的问题。几种与损伤相关的分子模式分子已被证明可诱发NETosis和血栓形成，其中高迁移率的第1号方盒（HMGB1）起着至关重要的作用。这篇综述讨论了NETosis和血栓形成及其在各种与血栓形成相关的疾病中的串扰，重点是HMGB1作为中风介导者的作用。我们还解决了与NETGB引起的血栓形成中HMGB1相互作用的肽基精氨酸脱亚氨酶4的功能。高移动性的第1号箱（HMGB1）扮演着至关重要的角色。这篇综述讨论了NETosis和血栓形成及其在各种与血栓形成相关的疾病中的串扰，重点是HMGB1作为中风介导者的作用。我们还解决了与NETGB引起的血栓形成中HMGB1相互作用的肽基精氨酸脱亚氨酶4的功能。高移动性的第1号箱（HMGB1）扮演着至关重要的角色。这篇综述讨论了NETosis和血栓形成及其在各种与血栓形成相关的疾病中的串扰，重点是HMGB1作为中风介导者的作用。我们还解决了与NETGB引起的血栓形成中HMGB1相互作用的肽基精氨酸脱亚氨酶4的功能。