Rani Meenakshi, Nicholson Susannah E, Zhang Qiong, Schwacha Martin G
Department of Surgery, The University of Texas Health Science Center at San Antonio, TX 78229, United States.
Department of Surgery, The University of Texas Health Science Center at San Antonio, TX 78229, United States; US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, United States.
Burns. 2017 Mar;43(2):297-303. doi: 10.1016/j.burns.2016.10.001. Epub 2016 Oct 27.
Burns are associated with activation of the innate immunity that can contribute to complications. Damage-associated molecular patterns (DAMPs) released after tissue injury play a critical role in the activation of the innate immunity, which appears to be mediated via toll-like receptors (TLRs). Previous findings have shown that TLRs and TLR-mediated responses are up-regulated after burn. Nonetheless, it is unclear what impact burn has on circulating levels of DAMPs. To study this, male C57BL/6 mice were subjected to a major burn or sham procedure. Three hours to 7days thereafter, plasma was collected and assayed for the representative DAMPs (i.e., HMGB1, cytochrome C, DNA and S100A) and extracellular cleavage products (fibronectin and hyaluronan). HMGB1, cytochrome C, fibronectin and hyaluronan levels were elevated in a time-dependent manner after burn as compared to sham levels. A significant elevation in TNF-α, IL-6 and IL-10 cytokine plasma levels was also found after burn. All cytokine levels were increased as early as 3h and remained elevated up to 24h. Circulating CD11b monocytes were increased at 24h after burn and showed increased expression of TLR-2. In conclusion, these findings support the concept that burn-induced elevations in circulating DAMPs are in part responsible for monocyte activation and the development of inflammatory complications under such conditions and warrants further investigation.
烧伤与可导致并发症的固有免疫激活有关。组织损伤后释放的损伤相关分子模式(DAMPs)在固有免疫激活中起关键作用,这似乎是通过Toll样受体(TLRs)介导的。先前的研究结果表明,烧伤后TLRs和TLR介导的反应会上调。然而,尚不清楚烧伤对DAMPs循环水平有何影响。为了研究这一点,对雄性C57BL/6小鼠进行大面积烧伤或假手术。此后3小时至7天,收集血浆并检测代表性的DAMPs(即高迁移率族蛋白B1、细胞色素C、DNA和S100A)以及细胞外裂解产物(纤连蛋白和透明质酸)。与假手术组相比,烧伤后HMGB1、细胞色素C、纤连蛋白和透明质酸水平呈时间依赖性升高。烧伤后还发现血浆中TNF-α、IL-6和IL-10细胞因子水平显著升高。所有细胞因子水平早在3小时就升高,并持续升高至24小时。烧伤后24小时循环中的CD11b单核细胞增加,并显示TLR-2表达增加。总之,这些发现支持了这样一种观点,即烧伤诱导的循环DAMPs升高在一定程度上导致了单核细胞激活以及在此类情况下炎症并发症的发生,值得进一步研究。