Huber-Lang Markus S, Ignatius Anita, Köhl Jörg, Mannes Marco, Braun Christian Karl
Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany.
Institue of Orthopaedic Research and Biomechanics, University Hospital of Ulm, Ulm, Germany.
Br J Pharmacol. 2021 Jul;178(14):2863-2879. doi: 10.1111/bph.15245. Epub 2020 Oct 27.
Physical trauma represents a major global burden. The trauma-induced response, including activation of the innate immune system, strives for regeneration but can also lead to post-traumatic complications. The complement cascade is rapidly activated by damaged tissue, hypoxia, exogenous proteases and others. Activated complement can sense, mark and clear both damaged tissue and pathogens. However, excessive and insufficient activation of complement can result in a dysfunctional immune and organ response. Similar to acute coagulopathy, complementopathy can develop with enhanced anaphylatoxin generation and an impairment of complement effector functions. Various remote organ effects are induced or modulated by complement activation. Frequently, established trauma treatments are double-edged. On one hand, they help stabilising haemodynamics and oxygen supply as well as injured organs and on the other hand, they also drive complement activation. Immunomodulatory approaches aim to reset trauma-induced disbalance of complement activation and thus may change surgical trauma management procedures to improve outcome. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.
身体创伤是一项重大的全球负担。创伤诱导的反应,包括先天免疫系统的激活,旨在促进再生,但也可能导致创伤后并发症。受损组织、缺氧、外源性蛋白酶等可迅速激活补体级联反应。激活的补体能够识别、标记并清除受损组织和病原体。然而,补体的过度激活和激活不足都可能导致免疫和器官反应功能失调。与急性凝血病类似,补体病可因过敏毒素生成增加和补体效应器功能受损而发生。补体激活可诱导或调节各种远隔器官效应。通常,既定的创伤治疗方法是一把双刃剑。一方面,它们有助于稳定血流动力学和氧气供应以及受损器官,另一方面,它们也会驱动补体激活。免疫调节方法旨在重置创伤诱导的补体激活失衡,因此可能会改变手术创伤管理程序以改善治疗结果。相关文章:本文是关于补体系统在健康和疾病中的经典与非经典功能的主题问题的一部分。要查看本节中的其他文章,请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc。