Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FASEB J. 2011 Feb;25(2):561-8. doi: 10.1096/fj.10-170027. Epub 2010 Oct 19.
Acute inflammation in healthy individuals is self-limiting and has an active termination program. The mechanisms by which acute inflammation is resolved are of interest. In murine zymosan-induced peritonitis, we found that eosinophils are recruited to the inflamed loci during the resolution phase of acute inflammation. In vivo depletion of eosinophils caused a resolution deficit, namely impaired lymphatic drainage with reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph node, and sustained numbers of polymorphonuclear leukocytes in inflamed tissues. Liquid chromatography-tandem mass spectrometry-based lipidomics of the resolving exudates revealed that locally activated eosinophils in the resolution phase produced proresolving mediators, including protectin D1 (PD1) from docosahexaenoic acid. The resolution deficit caused by eosinophil depletion was rescued by eosinophil restoration or the administration of PD1. Eosinophils deficient in 12/15-lipoxygenase could not rescue the resolution phenotype. The present results indicate that mouse eosinophils and eosinophil-derived lipid mediators, including PD1, have a role in promoting the resolution of acute inflammation, expanding the roles of eosinophils in host defense and resolution.
健康个体的急性炎症具有自限性和主动终止程序。人们对急性炎症消退的机制很感兴趣。在鼠类酵母聚糖诱导的腹膜炎中，我们发现嗜酸性粒细胞在急性炎症消退阶段被募集到炎症部位。体内嗜酸性粒细胞耗竭导致消退缺陷，即淋巴引流受损，吞噬了吞噬酵母聚糖的吞噬细胞在引流淋巴结中的出现减少，以及炎症组织中多形核白细胞数量持续增加。基于液相色谱-串联质谱的解析渗出物脂质组学分析显示，在消退阶段局部激活的嗜酸性粒细胞产生了促消退介质，包括来自二十二碳六烯酸的保护素 D1（PD1）。嗜酸性粒细胞耗竭引起的消退缺陷可通过嗜酸性粒细胞恢复或 PD1 给药得到挽救。缺乏 12/15-脂氧合酶的嗜酸性粒细胞不能挽救消退表型。这些结果表明，鼠类嗜酸性粒细胞和嗜酸性粒细胞衍生的脂质介质，包括 PD1，在促进急性炎症消退方面发挥作用，扩大了嗜酸性粒细胞在宿主防御和消退中的作用。
