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Endothelial cells, neutrophils and platelets: getting to the bottom of an inflammatory triangle
Open Biology ( IF 5.8 ) Pub Date : 2020-10-14 , DOI: 10.1098/rsob.200161
Tima Dehghani 1 , Alyssa Panitch 1
Affiliation  

Severe fibrotic and thrombotic events permeate the healthcare system, causing suffering for millions of patients with inflammatory disorders. As late-state consequences of chronic inflammation, fibrosis and thrombosis are the culmination of pathological interactions of activated endothelium, neutrophils and platelets after vessel injury. Coupling of these three cell types ensures a pro-coagulant, cytokine-rich environment that promotes the capture, activation and proliferation of circulating immune cells and recruitment of key pro-fibrotic cell types such as myofibroblasts. As the first responders to sterile inflammatory injury, it is important to understand how endothelial cells, neutrophils and platelets help create this environment. There has been a growing interest in this intersection over the past decade that has helped shape the development of therapeutics to target these processes. Here, we review recent insights into how neutrophils, platelets and endothelial cells guide the development of pathological vessel repair that can also result in underlying tissue fibrosis. We further discuss recent efforts that have been made to translate this knowledge into therapeutics and provide perspective as to how a compound or combination therapeutics may be most efficacious when tackling fibrosis and thrombosis that is brought upon by chronic inflammation.



中文翻译:

内皮细胞、中性粒细胞和血小板:到达炎症三角形的底部

严重的纤维化和血栓形成事件渗透到医疗保健系统中,给数百万患有炎症性疾病的患者带来痛苦。作为慢性炎症的晚期后果,纤维化和血栓形成是血管损伤后活化的内皮、中性粒细胞和血小板病理相互作用的结果。这三种细胞类型的偶联确保了促凝剂、富含细胞因子的环境,促进循环免疫细胞的捕获、激活和增殖以及关键促纤维化细胞类型(如肌成纤维细胞)的募集。作为无菌性炎症损伤的第一反应者,了解内皮细胞、中性粒细胞和血小板如何帮助创造这种环境非常重要。在过去的十年中,人们对这一交叉点越来越感兴趣,这有助于塑造针对这些过程的治疗方法的发展。在这里,我们回顾了最近关于中性粒细胞、血小板和内皮细胞如何引导病理性血管修复发展的见解,后者也可能导致潜在的组织纤维化。我们进一步讨论了最近为将这些知识转化为治疗所做的努力,并提供了关于化合物或联合治疗在解决慢性炎症引起的纤维化和血栓形成时如何最有效的观点。

更新日期:2020-10-15
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