DPAn-3 衍生的 13 系列 resolvins 的生物合成
中文名称
通路描述
中性粒细胞粘附于血管内皮是先天免疫反应中损伤或入侵病原体时的关键和早期事件(Sadik 等,2011)。对中性粒细胞 - 内皮细胞培养物的脂质分层的分析发现了四种新型 specialised proresolving mediators(SPMs)(Dalli 等,2015)。使用化学合成的前体(13(R)-羟基-DPAn-3)进行的 LC/MS-MS 代谢脂质组学分析鉴定出从该前体生成的四种介质。
多不饱和脂肪酸(PUFA)DPAn-3(cis-7,10,13,16,19-二十碳五烯酸)是二十二碳五烯酸(DHA)从二十碳五烯酸(EPA)生物合成的中间体,也是新型生物活性介质产生的前体。DPAn-3 在环氧化酶 2(COX2)的作用下可以形成该前体。因此,这些新型 13 系列 resolvins(RvT1-4)源自 DPAn-3(Primdahl 等,2016)。在 E. coli 感染的小鼠中,RvTs 加速了炎症的消退并增加了生存率。RvTs 还调节人类和鼠类吞噬细胞反应,刺激细菌吞噬和调节炎症小体成分(Dalli 等,2015)。这些 RvTs 的生物合成途径描述如下。RvTs 的形成需要中性粒细胞 - 内皮细胞相互作用,被认为通过两步过程进行;COX2 羟基化 DPAn-3 为 13(R)-DPAn-3,该物质转运到相邻的中性粒细胞,并被 5-脂氧合酶脂氧合化为 RvT1-4(Vik 等,2017)。
多不饱和脂肪酸(PUFA)DPAn-3(cis-7,10,13,16,19-二十碳五烯酸)是二十二碳五烯酸(DHA)从二十碳五烯酸(EPA)生物合成的中间体,也是新型生物活性介质产生的前体。DPAn-3 在环氧化酶 2(COX2)的作用下可以形成该前体。因此,这些新型 13 系列 resolvins(RvT1-4)源自 DPAn-3(Primdahl 等,2016)。在 E. coli 感染的小鼠中,RvTs 加速了炎症的消退并增加了生存率。RvTs 还调节人类和鼠类吞噬细胞反应,刺激细菌吞噬和调节炎症小体成分(Dalli 等,2015)。这些 RvTs 的生物合成途径描述如下。RvTs 的形成需要中性粒细胞 - 内皮细胞相互作用,被认为通过两步过程进行;COX2 羟基化 DPAn-3 为 13(R)-DPAn-3,该物质转运到相邻的中性粒细胞,并被 5-脂氧合酶脂氧合化为 RvT1-4(Vik 等,2017)。
英文描述
Biosynthesis of DPAn-3-derived 13-series resolvins Neutrophils adherence to the vascular endothelium is a critical and early event in the innate immune response to injury or invading pathogens (Sadik et al. 2011). Studies of the lipid fraction from neutrophil-endothelial cell cultures resulted in the discovery of four novel specialised proresolving mediators (SPMs) (Dalli et al. 2015). Results from LC/MS-MS metabololipidomics using a chemically-synthesised precursor (13(R)-hydroxy-DPAn-3) identified four mediators generated from this precursor.
The polyunsaturated fatty acid (PUFA) Ï-3 cis-7,10,13,16,19-docosapentaenoic acid (DPAn-3) is an intermediate in the biosynthesis of docosahexaenoic acid (DHA) from eicosapentaenoic acid (EPA) and is also a precursor for the production of novel bioactive mediators. DPAn-3 can form this precursor when acted upon by cyclooxygenase 2 (COX2). Thus these novel 13-series resolvins (RvT1-4) originate from DPAn-3 (Primdahl et al. 2016). In E. coli-infected mice, RvTs accelerated resolution of inflammation and increased survival. RvTs also regulated human and mouse phagocyte responses, stimulating bacterial phagocytosis and regulating inflammasome components (Dalli et al. 2015). The biosynthetic routes of these RvTs are described here. RvT formation requires neutrophil-endothelial cell interaction and is thought to proceed via a two-step process; COX2 hydroxylates DPAn-3 to 13(R)-DPAn-3 which trafficks to adjacent neutrophils where it is lipoxygenated by 5-lipoxygenase to RvT1-4 (Vik et al. 2017).
The polyunsaturated fatty acid (PUFA) Ï-3 cis-7,10,13,16,19-docosapentaenoic acid (DPAn-3) is an intermediate in the biosynthesis of docosahexaenoic acid (DHA) from eicosapentaenoic acid (EPA) and is also a precursor for the production of novel bioactive mediators. DPAn-3 can form this precursor when acted upon by cyclooxygenase 2 (COX2). Thus these novel 13-series resolvins (RvT1-4) originate from DPAn-3 (Primdahl et al. 2016). In E. coli-infected mice, RvTs accelerated resolution of inflammation and increased survival. RvTs also regulated human and mouse phagocyte responses, stimulating bacterial phagocytosis and regulating inflammasome components (Dalli et al. 2015). The biosynthetic routes of these RvTs are described here. RvT formation requires neutrophil-endothelial cell interaction and is thought to proceed via a two-step process; COX2 hydroxylates DPAn-3 to 13(R)-DPAn-3 which trafficks to adjacent neutrophils where it is lipoxygenated by 5-lipoxygenase to RvT1-4 (Vik et al. 2017).
所含基因
1 个基因