Department of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USA.
J Biomed Sci. 2011 Nov 30;18(1):90. doi: 10.1186/1423-0127-18-90.
Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
创伤是工业化国家年轻人死亡的主要原因。最近的临床和实验研究越来越多地证明，固有免疫系统的激活有助于创伤后后遗症和不良后果的发病机制。作为“第一道防线”，补体系统代表固有免疫的有效效应臂，并被认为介导创伤后早期炎症反应。尽管补体具有一般的有益功能，包括病原体清除和对危险信号的即时反应，但在创伤后，补体激活可能会对宿主组织产生有害影响，从而对宿主组织造成“无辜旁观者”的攻击。创伤后缺血/再灌注损伤代表补体介导的组织损伤的经典实体，通过加剧局部和全身炎症以及释放毒性介质来增加“抗原负荷”。这些病理生理后果被证明在重大创伤后维持全身炎症反应综合征，并最终导致远处器官损伤和死亡。近年来设计了许多实验模型，旨在模拟创伤后的炎症反应，并允许测试新的药物治疗方法，包括新兴的靶向补体抑制的概念。本文综述了对重大创伤后补体激活的细胞和分子机制的当前理解，并强调了新兴的治疗概念，这些概念可能为未来药物治疗策略的“基础到临床”设计提供依据。
