Mitochondrial-derived N-formyl peptides: novel links between trauma, vascular collapse and sepsis.
Mitochondrial-derived N-formyl peptides: novel links between trauma, vascular collapse and sepsis.
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DOI：
10.1016/j.mehy.2013.06.026
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发表时间：
2013-10
影响因子：
4.7
通讯作者：
Webb, R. C.
中科院分区：
文献类型：
--
作者：
Wenceslau, C. F.;McCarthy, C. G.;Goulopoulou, S.;Szasz, T.;NeSmith, E. G.;Webb, R. C.
脓毒症是创伤患者死亡率和发病率的主要原因，尽管积极治疗。创伤性损伤可引发感染性或非感染性全身炎症反应综合征（SIRS）和败血症。脓毒症和SIRS伴有无法调节炎症反应，但这种扰动的原因尚不清楚。脓毒症的主要病理生理特征是血管塌陷（即血管张力失去控制）；然而，在细胞水平上，极端血管舒张的最终介质尚未确定。创伤后，细胞损伤释放内源性损伤相关分子模式（DAMPs），激活先天免疫系统。线粒体DAMPs表达至少两种分子特征，分别作用于甲酰基肽受体（FPRs）和toll样受体9的n -甲酰基肽和线粒体DNA。n -甲酰基肽是有效的免疫细胞激活剂，一旦在循环中释放，它们通过尚未完全了解的细胞机制诱导血管张力调节。我们已经观察到，来自细菌（FMLP）和线粒体（FMIT）来源的n -甲酰基肽可诱导fpr介导的血管舒张。因此，我们提出组织和细胞创伤诱导线粒体释放n -甲酰基肽，通过激活FPR引发炎症和血管塌陷，并促进败血症的发展。提出的假设提供了具有临床意义的信息，将创伤、线粒体n -甲酰基肽和炎症与血管塌陷和败血症联系起来。如果我们的假设是正确的，它可能会导致脓毒症管理的新策略，可以帮助临床医生有效地管理非感染性和感染性炎症反应。
Sepsis is a major cause of mortality and morbidity in trauma patients despite aggressive treatment. Traumatic injury may trigger infective or non-infective systemic inflammatory response syndrome (SIRS) and sepsis. Sepsis and SIRS are accompanied by an inability to regulate the inflammatory response but the cause of this perturbation is still unknown. The major pathophysiological characteristic of sepsis is the vascular collapse (i.e., loss of control of vascular tone); however, at the cellular level the final mediator of extreme vasodilatation has yet to be identified. After trauma, cellular injury releases endogenous damage-associated molecular patterns (DAMPs) that activate the innate immune system. Mitochondrial DAMPs express at least two molecular signatures, N-formyl peptides and mitochondrial DNA that act on formyl peptide receptors (FPRs) and Toll-like receptor 9, respectively. N-Formyl peptides are potent immunocyte activators and, once released in the circulation, they induce modulation of vascular tone by cellular mechanisms that are not completely understood. We have observed that N-formyl peptides from bacterial (FMLP) and mitochondrial (FMIT) sources induce FPR-mediated vasodilatation in resistance arteries. Accordingly, we propose that tissue and cellular trauma induces the release of N-formyl peptides from mitochondria triggering inflammation and vascular collapse via activation of FPR and contributing to the development of sepsis. The proposed hypothesis provides clinically significant information linking trauma, mitochondrial N-formyl peptides and inflammation to vascular collapse and sepsis. If our hypothesis is true, it may lead to new strategies in the management of sepsis that can help clinicians effectively manage non-infectious and infectious inflammatory responses.
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影响因子：
3.1
作者：
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通讯作者：
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通讯作者：
FORSTERMANN, U
影响因子：
15.3
作者：
HaimovitzFriedman, A;CordonCardo, C;Kolesnick, R
通讯作者：
Kolesnick, R