Mitochondrial DNA in Sepsis.
Mitochondrial DNA in Sepsis.
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DOI：
10.1097/mcc.0000000000000427
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发表时间：
2017-08
影响因子：
3.3
通讯作者：
Nakahira K
中科院分区：
文献类型：
--
作者：
Harrington JS;Choi AMK;Nakahira K
随着我们更好地了解病原体相关分子模式 (PAMP) 和损伤相关分子模式 (DAMP) 对疾病发病机制的影响，我们对危重疾病的理解正在发生转变。在已知的 DAMP 中，人们对线粒体 DNA (mtDNA) 越来越感兴趣，因为它能够传播脓毒症和其他病症中的炎症反应。在这篇综述中，我们描述了 mtDNA 从线粒体转移到细胞质和细胞外空间的不同机制，在这些机制中它可以引发炎症反应。此外，我们还介绍了一些最新的临床研究，以检查危重疾病中的 mtDNA。基础科学研究提供了令人信服的数据，证明 mtDNA 可以通过 Toll 样受体 9 和炎症小体影响免疫系统。临床试验提供的证据表明，危重患者的 mtDNA 升高，并且与死亡率相关。虽然 mtDNA 是一种 DAMP，在许多情况下都会升高，但这一发现的临床影响仍然难以捉摸。需要进一步的工作来确定 mtDNA 是否可以用作疾病严重程度或死亡率的生物标志物。
Our understanding of critical illness is transforming as we develop a better understanding of the impact pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) have on the pathogenesis of disease. Of the known DAMPs, there is a growing interest in mitochondrial DNA (mtDNA) as a DAMP capable of propagating the inflammatory response seen in sepsis and other conditions. In this review, we describe the varying mechanisms by which mtDNA is translocated from mitochondria into cytosol and the extracellular space where it can illicit an inflammatory response. Additionally, we present some of the most recent clinical studies to examine mtDNA in critical illness. Basic science research provides convincing data that mtDNA can influence the immune system through toll-like receptor 9 and inflammasomes. Clinical trials provide evidence that mtDNA is elevated in critically ill patients, and is associated with mortality. While mtDNA is a DAMP shown to be elevated in numerous conditions the clinical ramifications of this finding remain elusive. Further work is needed to determine if mtDNA can be utilized as a biomarker of disease severity or mortality.