Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Am J Physiol Cell Physiol. 2014 Jul 1;307(1):C39-54. doi: 10.1152/ajpcell.00024.2014. Epub 2014 Apr 2.
Resolution of acute inflammation is an active process locally controlled by a novel genus of specialized pro-resolving mediators (SPM) that orchestrate key resolution responses. Hence, it is of general interest to identify individual bioactive mediators and profile their biosynthetic pathways with related isomers as well as their relation(s) to classic eicosanoids in mammalian tissues. Lipid mediator (LM)-SPM levels and signature profiles of their biosynthetic pathways were investigated using liquid chromatography-tandem mass spectrometry (LC-MS-MS)-based LM metabololipidomics. LM and SPM were identified using ≥6 diagnostic ions and chromatographic behavior matching with both authentic and synthetic materials. This approach was validated using the composite reference plasma (SRM1950) of 100 healthy individuals. Using targeted LM metabololipidomics, we profiled LM and SPM pathways in human peripheral blood (plasma and serum) and lymphoid organs. In these, we identified endogenous SPM metabolomes, namely, the potent lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR). These included RvD1, RvD2, RvD3, MaR1, and NPD1/PD1, which were identified in amounts within their bioactive ranges. In plasma and serum, principal component analysis (PCA) identified signature profiles of eicosanoids and SPM clusters. Plasma-SPM increased with omega-3 and acetylsalicylic acid intake that correlated with increased phagocytosis of Escherichia coli in whole blood. These findings demonstrate an approach for identification of SPM pathways (e.g., resolvins, protectins, and maresins) in human blood and lymphoid tissues that were in amounts commensurate with their pro-resolving, organ protective, and tissue regeneration functions. LM metabololipidomics coupled with calibration tissues and physiological changes documented herein provide a tool for functional phenotypic profiling.
急性炎症的消退是一个局部的主动过程，由一类新型的专门的促解决介质（SPM）来控制，这些介质协调了关键的消退反应。因此，确定个体生物活性介质并分析其生物合成途径及其相关异构体，以及它们与哺乳动物组织中经典类二十烷酸的关系，是很有意义的。采用基于液相色谱-串联质谱（LC-MS-MS）的脂质代谢组学方法，研究了脂质介质（LM）-SPM 水平及其生物合成途径的特征图谱。采用≥6 个诊断离子，以及与真实和合成材料相匹配的色谱行为，鉴定了 LM 和 SPM。该方法使用 100 名健康个体的复合参考血浆（SRM1950）进行了验证。采用靶向脂质代谢组学，我们对人外周血（血浆和血清）和淋巴器官中的 LM 和 SPM 途径进行了分析。在这些组织中，我们鉴定了内源性 SPM 代谢组，即强效脂氧素（LX）、消退素（Rv）、保护素（PD）和maresin（MaR）。其中包括 RvD1、RvD2、RvD3、MaR1 和 NPD1/PD1，它们的含量处于生物活性范围内。在血浆和血清中，主成分分析（PCA）确定了类二十烷酸和 SPM 簇的特征图谱。血浆 SPM 随着 ω-3 和乙酰水杨酸的摄入而增加，这与全血中大肠杆菌吞噬作用的增加相关。这些发现表明，采用一种方法可以鉴定人血液和淋巴组织中的 SPM 途径（如消退素、保护素和maresin），其含量与它们的促解决、器官保护和组织再生功能相当。本文结合校准组织和生理变化，提供了一种用于功能表型分析的 LM 代谢组学工具。
