Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA.
Front Immunol. 2012 Apr 17;3:81. doi: 10.3389/fimmu.2012.00081. eCollection 2012.
Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA). Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered forms of protectins (AT-PD1). The new oxygenated DHEA-derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor) and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN) recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.
内源性机制对于成功解决急性炎症反应和局部恢复内稳态很重要，因为过度炎症是许多人类疾病的基础。在这篇综述中，我们提供了功能代谢组学的最新概述，该研究确定了二十二碳六烯酸 (DHA) 的新生物活性代谢组。系统研究表明，DHA 被转化为 DHEA 衍生的新型生物活性产物以及阿司匹林触发的保护素 (AT-PD1)。新的氧化 DHEA 衍生产物可阻止 PMN 趋化，降低 P-选择素表达和血小板白细胞黏附，并在缺血/再灌注损伤中显示出器官保护作用。这些产物激活了大麻素受体 (CB2 受体)，而不是 CB1 受体。AT-PD1 减少了鼠腹膜炎中的中性粒细胞 (PMN) 募集。用人细胞时，AT-PD1 减少了跨内皮 PMN 迁移，并增强了巨噬细胞对凋亡人 PMN 的吞噬作用。这里综述的最新发现表明，DHEA 氧化代谢和阿司匹林触发的 DHA 转化产生了具有抗炎和器官保护特性的强效新型分子，开辟了 DHA 代谢组的功能作用。
