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Thorax:内源性线粒体甲酰肽在急性呼吸窘迫综合征中的作用!

2017-05-04 xing.T MedSci原创

该研究首次提供了确凿的证据表明线粒体甲酰肽在人类疾病中发挥作用,并且证实了它在ARDS患者表达有所增加,以及在肺损伤的小鼠模型中发挥重要作用。这项工作揭示了线粒体甲酰肽FPR1信号作为无菌性急性肺损伤的关键驱动因素,并且可以作为ARDS的潜在治疗靶点。

急性呼吸窘迫综合征(ARDS)是一种致命的中性粒细胞占主导的肺部疾病。虽然受多种炎症介质的影响,确定识别合适的治疗候选分子仍不明确。近日,胸部疾病领域权威杂志Thorax上发表了一篇研究文章,研究人员旨在明确线粒体甲酰肽是否存在于急性呼吸窘迫综合征的患者中,并明确甲酰肽受体1(FPR1)信号在无菌性炎症中的重要功能。

研究人员采用液相色谱串联质谱的方法来确定ARDS患者支气管肺泡灌洗液(BALF)和血清中有无线粒体甲酰肽的存在。在体外培养实验中,研究人员采用线粒体甲酰肽刺激人中性粒细胞,以及采用流式细胞仪和趋化试验来评估其效应。研究人员采用线粒体甲酰肽或盐酸诱导小鼠肺损伤,采用骨髓嵌合体来明确骨髓和实质的FPR1对肺部无菌性炎症的作用。

研究人员发现ARDS患者BALF和血清中线粒体甲酰肽水平升高,在体外和体内实验中,这些肽可以通过FPR1依赖机制驱动中性粒细胞激活以及趋化性。在小鼠肺损伤中,FPR1-/-小鼠的炎症反应减弱。FPR1表达在肺泡上皮和嵌合体小鼠中,表明骨髓和实质FPR1均可以促进肺部炎症。

该研究首次提供了确凿的证据表明线粒体甲酰肽在人类疾病中发挥作用,并且证实了它在ARDS患者表达有所增加,以及在肺损伤的小鼠模型中发挥重要作用。这项工作揭示了线粒体甲酰肽FPR1信号作为无菌性急性肺损伤的关键驱动因素,并且可以作为ARDS的潜在治疗靶点。

原始出处:

David A Dorward, et al.Novel role for endogenous mitochondrial formylated peptide-driven formyl peptide receptor 1 signalling in acute respiratory distress syndrome.Thorax. 2017. http://dx.doi.org/10.1136/thoraxjnl-2017-210030

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