Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue
Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue
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DOI：
10.1152/ajpcell.00024.2014
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发表时间：
2014-07-01
影响因子：
5.5
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
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作者：
Colas, Romain A.;Shinohara, Masakazu;Serhan, Charles N.
急性炎症的消退是一个主动过程，由一种新的专门的促消退介质（SPM）局部控制，该介质协调关键的消退反应。因此，它是普遍感兴趣的，以确定个人的生物活性介质和概况其生物合成途径与相关的异构体，以及它们的关系（S）经典cicosanoids在哺乳动物组织。脂质介质（LM）-SPM的水平和签名配置文件的生物合成途径进行了研究，使用液相色谱-串联质谱（LC-MS-MS）为基础的LM代谢脂质组学。LM和SPM使用>= 6个诊断离子和与真实和合成材料匹配的色谱行为进行鉴定。使用100名健康个体的复合参比血浆（SRM 1950）对该方法进行了验证。使用靶向LM代谢脂质组学，我们分析了人外周血（血浆和血清）和淋巴器官中的LM和SPM通路。在这些研究中，我们鉴定了内源性SPM代谢组，即有效的脂氧素（LX）、消退素（Rv）、保护素（PD）和maresins（MaR）。这些包括RvD 1、RvD 2、RvD 3、MaR 1和NPD 1/PD 1，其含量在其生物活性范围内。在血浆和血清中，主成分分析（PCA）确定了类花生酸和SPM簇的特征谱。血浆SPM增加与ω-3和乙酰水杨酸摄入量，增加吞噬大肠杆菌在全血中。这些发现证明了一种鉴定SPM途径的方法（例如，消退素、保护素和maresins），其量与其促消退、器官保护和组织再生功能相当。LM代谢脂质组学结合本文记录的校准组织和生理变化提供了功能表型分析的工具。
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 cicosanoids 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.