Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden.
Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden.
Thromb Res. 2018 Apr;164 Suppl 1:S148-S152. doi: 10.1016/j.thromres.2018.01.049.
In addition to the central role of platelets in hemostasis, they contribute to pathological conditions such as inflammation and tumor progression. Aberrant expression and/or exposure of pro-coagulant factors in the tumor microenvironment induce platelet activation and subsequent release of growth factors from platelet granules. Cancer patients are commonly affected by thrombotic events, as a result of tumor-induced platelet activation. A novel player potentially contributing to cancer-associated thrombosis is the formation of neutrophil extracellular traps (NETs). NETs are composed of externalized DNA of nuclear or mitochondrial origin, bound to histones and granular proteases such as neutrophil elastase (NE) and myeloperoxidase (MPO). These extracellular traps help neutrophils to catch and kill pathogens such as bacteria, virus and fungi. It is now clear that NETs form also under conditions of sterile inflammation such as cancer and autoimmunity and can promote thrombosis. Recent data show that platelets play a key role in determining when and where NETs should form. This review will highlight our current insight in the role of platelets as regulators of NET formation, both during infection and sterile inflammation.
除了在止血中的核心作用外，血小板还参与炎症和肿瘤进展等病理状态。肿瘤微环境中促凝因子的异常表达和/或暴露会诱导血小板活化，随后血小板颗粒释放生长因子。由于肿瘤诱导的血小板活化，癌症患者常发生血栓栓塞事件。一种可能导致癌症相关血栓形成的新的参与者是中性粒细胞胞外诱捕网（NETs）的形成。NETs 由核或线粒体来源的外化 DNA 组成，与组蛋白和颗粒蛋白酶（如中性粒细胞弹性蛋白酶（NE）和髓过氧化物酶（MPO））结合。这些细胞外陷阱有助于中性粒细胞捕获和杀死细菌、病毒和真菌等病原体。现在已经清楚，NETs 在癌症和自身免疫等无菌炎症条件下也会形成，并可促进血栓形成。最近的数据表明，血小板在决定 NETs 何时何地形成方面起着关键作用。这篇综述将重点介绍我们目前对血小板作为 NET 形成的调节剂的作用的认识，包括在感染和无菌炎症期间。
