Formyl Peptide Receptor Activation Elicits Endothelial Cell Contraction and Vascular Leakage.
Formyl Peptide Receptor Activation Elicits Endothelial Cell Contraction and Vascular Leakage.
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DOI：
10.3389/fimmu.2016.00297
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发表时间：
2016
影响因子：
7.3
通讯作者：
Webb RC
中科院分区：
文献类型：
--
作者：
Wenceslau CF;McCarthy CG;Webb RC
全身炎症反应综合征(SIRS)和脓毒症的主要病理生理特征是血管张力失控和内皮屏障功能障碍。这些变化归因于促炎介质。有人提出，在没有感染的患者和大鼠中，受损组织中的细胞成分是血管损伤的主要煽动者。线粒体与细菌有几个共同的特征，当线粒体片段在受伤后被释放到循环中时，它们被先天性免疫系统识别。N-甲酰基多肽是细菌和线粒体的常见分子标志，已知通过激活甲酰基多肽受体(FPR)在炎症的启动中发挥作用。我们已经证明，输注线粒体N-甲酰肽(F-MIT)会导致脓毒症样症状，包括血管渗漏。我们还观察到，F-MIT通过激活FPR，引起内皮细胞细胞骨架调节蛋白的变化。因此，我们假设这些由FPR介导的细胞骨架变化可以导致内皮细胞收缩，从而导致血管渗漏。在这里，我们认为内皮细胞fpr是创伤后SIRS和脓毒症患者屏障功能受损的关键因素。
The major pathophysiological characteristic of systemic inflammatory response syndrome (SIRS) and sepsis is the loss of control of vascular tone and endothelial barrier dysfunction. These changes are attributed to pro-inflammatory mediators. It has been proposed that in patients and rats without infection, cell components from damaged tissue are the primary instigators of vascular damage. Mitochondria share several characteristics with bacteria, and when fragments of mitochondria are released into the circulation after injury, they are recognized by the innate immune system. N-Formyl peptides are common molecular signatures of bacteria and mitochondria and are known to play a role in the initiation of inflammation by activating the formyl peptide receptor (FPR). We have demonstrated that infusion of mitochondrial N-formyl peptides (F-MIT) leads to sepsis-like symptoms, including vascular leakage. We have also observed that F-MIT, via FPR activation, elicits changes in cytoskeleton-regulating proteins in endothelial cells. Therefore, we hypothesize that these FPR-mediated changes in cytoskeleton can cause endothelial cell contraction and, consequently vascular leakage. Here, we propose that endothelial FPR is a key contributor to impaired barrier function in SIRS and sepsis patients following trauma.