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Resolvin E1 and protectin D1 activate inflammation-resolution programmes

机译:Resolvin E1和protectin D1激活炎症缓解程序

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摘要

Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases—pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators—caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A_4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvEl and PD1 are potent agonists for resolution of inflamed tissues.
机译:急性炎症的解决是对适当的宿主反应,组织保护和恢复稳态必不可少的一个活跃过程。在拆分过程中,特定的omega-3多不饱和脂肪酸衍生的介体在拆分的分泌物中产生,包括resolvin E1(RvE1)和保护素D1(PD1)。因此,重要的是在调节组织分辨率中精确确定RvE1和PD1的特定作用。在这里我们报道RvE1和PD1纳克级通过调节白细胞浸润,增加体内和体外凋亡的多形核中性粒细胞的巨噬细胞摄取以及增强在吞噬淋巴结和脾脏中携带吞噬的酵母聚糖的吞噬细胞的外观来促进急性炎症过程中的吞噬细胞清除。在这种组织地形中,抑制环氧合酶或脂氧合酶(促炎性和分解性介体的暂时生成中的关键酶)会导致“分辨率不足”,RvE1,PD1或阿司匹林触发的脂蛋白A_4类似物可以挽救这种情况。此外,还确定了新的解决途径,涉及吞噬穿过遍及周围脂肪组织的吞噬细胞和携带吞噬的酵母聚糖到淋巴结的非凋亡多形核中性粒细胞。总之,这些结果确定了渗出后消融通行的新活性成分,并证明RvE1和PD1是消炎组织的有效激动剂。

著录项

  • 来源
    《Nature》 |2007年第7146期|p.869-874|共6页
  • 作者单位

    Klinik und Poliklinik fuer Neurologie & Experimentelle Neurologie, Campus-Mitte, Charite Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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
  • 中图分类 自然科学总论;
  • 关键词

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