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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways
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Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways

机译：因表达途径不同而引起的人类急性炎症反应的持续时间和严重程度二分法

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摘要

Lipoxins (Lxs) and aspirin-triggered epi-Lxs (15-epi-LxA_4) act through the ALX/FPRL1 receptor to block leukocyte trafficking, dampen cytokine/chemokine synthesis, and enhance phagocytic clearance of apoptotic leukocytes-key requisites for inflammatory resolution. Although studies using primarily inbred rodents have highlighted resolution as an active event, little is known about the role resolution pathways play in controlling the duration/profile of inflammatory responses in humans. To examine this, we found two types of responders to cantharidin-induced skin blisters in male healthy volunteers: those with immediate leukocyte accumulation and cytokine/chemokine synthesis followed by early resolution and a second group whose inflammation increased gradually over time followed by delayed resolution. In early resolvers, blister 15-epi-LxA_4 and leukocyte ALX were low, but increased as inflammation abated. In contrast, in delayed resolvers, 15-epi-LxA_4 and ALX were high early in the response but waned as inflammation progressed. Elevating 15-epi-LxA_4 in early resolvers using aspirin increased blister leukocyte ALX but reduced cytokines/chemokines as well as polymorphonuclear leukocyte and macrophage numbers. These findings show that two phenotypes exist in humans with respect to inflammation severity/longevity controlled by proresolution mediators, namely 15-epi-LxA_4. These data have implications for understanding the etiology of chronic inflammation and future directions in antiinflammatory therapy.
机译：脂蛋白（Lxs）和阿司匹林触发的Epi-Lxs（15-epi-LxA_4）通过ALX / FPRL1受体发挥作用，阻断白细胞运输，抑制细胞因子/趋化因子的合成，并增强吞噬清除凋亡白细胞的能力，这是解决炎症的关键条件。尽管主要使用近交啮齿类动物的研究强调了分辨率是一个活跃的事件，但是人们对于分辨率通路在控制人类炎症反应的持续时间/特征方面所起的作用知之甚少。为了检验这一点，我们在男性健康志愿者中发现了两种对依他那啶诱导的皮肤水疱的反应物：即刻具有白细胞积聚和细胞因子/趋化因子合成并随后早期消退的炎症反应；第二组炎症随着时间的推移逐渐增加，随后延迟消退。在早期的解析器中，水疱15-epi-LxA_4和白细胞ALX较低，但随着炎症减轻而增加。相反，在延迟解析器中，15-epi-LxA_4和ALX在反应早期较高，但随着炎症的进展而减弱。在早期使用阿司匹林的解析器中升高15-epi-LxA_4可增加水泡白细胞ALX，但减少细胞因子/趋化因子以及多形核白细胞和巨噬细胞数量。这些发现表明，在人类中，由高分辨率决议介质控制的炎症严重性/寿命的表型为15-epi-LxA_4。这些数据对于理解慢性炎症的病因和抗炎治疗的未来方向具有启示意义。

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    Thea Morris; Melanie Stables; Paul Colville-Nash; Justine Newson; Geoffrey Bellingan; Patricia M. de Souza; Derek W. Gilroy;

  • 作者单位

    Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom;

    Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom;

    South West Thames Institute for Renal Research, St. Helier Hospital, Carshalton SM5 1AA, United Kingdom;

    Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom;

    Critical Care, University College London Hospitals National Health Service Foundation Trust, London NW1 2BU, United Kingdom;

    Cardiothoracic Pharmacology Department, Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom;

    Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    eicosanoids; inflammation; leukocytes;

    机译：类花生酸;炎;白细胞;

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