Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation.
Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation.
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DOI：
10.1016/j.pupt.2016.02.005
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发表时间：
2016-04
影响因子：
3.2
通讯作者：
Webb, R. Clinton
中科院分区：
文献类型：
--
作者：
Wenceslau, Camilla Ferreira;Szasz, Theodora;McCarthy, Cameron G.;Baban, Babak;NeSmith, Elizabeth;Webb, R. Clinton
呼吸衰竭是全身炎症反应综合征(SIRS)和脓毒症的共同特征。创伤和严重失血导致内源性分子释放，称为损伤相关分子模式(DAMP)。线粒体N-甲酰基多肽(F-MITs)是一类与细菌N-甲酰基多肽有相似之处的物质，是一种有效的免疫系统激活剂。最近，我们观察到失血性休克引起的血浆F-MITs水平的升高与肺损伤有关，而甲酰肽受体(FPR)的拮抗可以改善失血性休克所致的大鼠肺损伤。证实了这些数据，在本研究中，观察到创伤SIRS或脓毒症患者的血浆样本中F-MITs的表达高于对照创伤组。因此，为了更好地了解F-MITs在调节肺和呼吸道功能中的作用，我们研究了F-MITs导致呼吸道收缩和肺部炎症的假说。我们观察到F-MITs在气管、支气管和细支气管处诱导浓度依赖的收缩。然而，肥大细胞脱颗粒剂或FPR拮抗剂的预处理可降低这一反应。最后，气管内注射F-MITs可增加中性粒细胞弹性蛋白酶在肺中的表达，以及诱导型一氧化氮合酶和细胞分裂控制蛋白42在所有气道节段的表达。这些数据表明，F-MITs可能是治疗创伤患者呼吸衰竭的潜在靶点。
Respiratory failure is a common characteristic of systemic inflammatory response syndrome (SIRS) and sepsis. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns (DAMPs). Mitochondrial N-formyl peptides (F-MITs) are DAMPs that share similarities with bacterial N-formylated peptides, and are potent immune system activators. Recently, we observed that hemorrhagic shock-induced increases in plasma levels of F-MITs associated with lung damage, and that antagonism of formyl peptide receptors (FPR) ameliorated hemorrhagic shock-induced lung injury in rats. Corroborating these data, in the present study, it was observed that F-MITs expression is higher in plasma samples from trauma patients with SIRS or sepsis when compared to control trauma group. Therefore, to better understand the role of F-MITs in the regulation of lung and airway function, we studied the hypothesis that F-MITs lead to airway contraction and lung inflammation. We observed that F-MITs induced concentration-dependent contraction in trachea, bronchi and bronchioles. However, pre-treatment with mast cells degranulator or FPR antagonist decreased this response. Finally, intratracheal challenge with F-MITs increased neutrophil elastase expression in lung and inducible nitric oxide synthase and cell division control protein 42 expression in all airway segments. These data suggest that F-MITs could be a putative target to treat respiratory failure in trauma patients.
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DOI：
10.1083/jcb.146.2.267
发表时间：
1999-07-26
期刊：
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影响因子：
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影响因子：
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作者：
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