Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna , Vienna , Austria ; INSERM UMR_S 1109, Laboratory of Excellence Transplantex, University of Strasbourg , Strasbourg , France ; German Academy of Transplantation Medicine, Munich , Germany ; and Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden , Dresden , Germany.
Physiol Rev. 2018 Apr 1;98(2):727-780. doi: 10.1152/physrev.00041.2016.
When cells undergo necrotic cell death in either physiological or pathophysiological settings in vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium and thereby represent the strongest known trigger of the immune system. With our increasing understanding of necrosis as a regulated and genetically determined process (RN, regulated necrosis), necrosis and necroinflammation can be pharmacologically prevented. This review discusses our current knowledge about signaling pathways of necrotic cell death as the origin of necroinflammation. Multiple pathways of RN such as necroptosis, ferroptosis, and pyroptosis have been evolutionary conserved most likely because of their differences in immunogenicity. As the consequence of necrosis, however, all necrotic cells release damage associated molecular patterns (DAMPs) that have been extensively investigated over the last two decades. Analysis of necroinflammation allows characterizing specific signatures for each particular pathway of cell death. While all RN-pathways share the release of DAMPs in general, most of them actively regulate the immune system by the additional expression and/or maturation of either pro- or anti-inflammatory cytokines/chemokines. In addition, DAMPs have been demonstrated to modulate the process of regeneration. For the purpose of better understanding of necroinflammation, we introduce a novel classification of DAMPs in this review to help detect the relative contribution of each RN-pathway to certain physiological and pathophysiological conditions.
当细胞在体内生理或病理生理环境中发生坏死性细胞死亡时，它们会将高度免疫原性的细胞内分子和细胞器释放到细胞间隙中，从而成为已知最强的免疫系统触发因素。随着我们对坏死作为一种受调控和基因决定的过程（RN，受调控的坏死）的理解不断增加，可以通过药理学手段预防坏死和坏死性炎症。这篇综述讨论了我们目前对坏死性细胞死亡信号通路作为坏死性炎症起源的认识。多种 RN 途径，如坏死性凋亡、铁死亡和细胞焦亡，在进化上是保守的，这很可能是因为它们在免疫原性上存在差异。然而，作为坏死的结果，所有坏死细胞都会释放损伤相关分子模式（DAMPs），这些模式在过去二十年中得到了广泛研究。坏死性炎症的分析可以为每种特定的细胞死亡途径特征化特定的特征。虽然所有的 RN 途径都普遍释放 DAMPs，但它们中的大多数通过额外表达和/或成熟促炎或抗炎细胞因子/趋化因子来主动调节免疫系统。此外，DAMPs 已被证明可以调节再生过程。为了更好地理解坏死性炎症，我们在这篇综述中引入了一种 DAMPs 的新分类方法，以帮助检测每个 RN 途径对某些生理和病理生理条件的相对贡献。
