PD(n-3 DPA) Pathway Regulates Human Monocyte Differentiation and Macrophage Function.
PD(n-3 DPA) Pathway Regulates Human Monocyte Differentiation and Macrophage Function.
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DOI：
10.1016/j.chembiol.2018.04.017
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发表时间：
2018-06-21
影响因子：
8.6
通讯作者：
Dalli J
中科院分区：
文献类型：
--
作者：
Pistorius K;Souza PR;De Matteis R;Austin-Williams S;Primdahl KG;Vik A;Mazzacuva F;Colas RA;Marques RM;Hansen TV;Dalli J
巨噬细胞在炎症过程中协调凋亡细胞和细胞碎片的清除中起核心作用，调节该过程的机制仍然令人感兴趣。在此，我们发现n-3二十二碳五烯酸衍生的保护素（PDn-3 DPA）生物合成途径调节人单核细胞的分化，改变巨噬细胞表型，巨噬细胞吞噬作用和细菌吞噬作用。使用脂质介质分析、人原代细胞和重组酶，我们发现人15-脂氧合酶启动催化烯丙基环氧化物形成的PDn-3 DPA途径。使用立体控制的全有机合成确定该环氧化物的完整立体化学为16 S，17 S-环氧-7Z，10 Z，12 E，14 E，19 Z-二十二碳五烯酸（16 S，17 S-ePDn-3 DPA）。该中间体通过环氧化物水解酶酶促转化为PD 1 n-3 DPA和PD 2n-3 DPA，环氧化物水解酶2在人单核细胞中将16 S，17 S-ePDn-3 DPA转化为PD 2n-3 DPA。总之，这些结果确立了人单核细胞和巨噬细胞中的PDn-3 DPA生物合成途径及其在调节巨噬细胞消退反应中的作用。PDn-3 DPA调节人单核细胞衍生的巨噬细胞分化和功能16 S，17 S-ePDn-3 DPA的形成和完整立体化学的证据EPHX 2在人单核细胞中将16 S，17 S-ePDn-3 DPA转化为PD 2n-3 DPA Pistorius等人，发现最近发现的称为PDn-3 DPA的生物活性介质家族在其从单核细胞分化期间控制人巨噬细胞表型和功能。作者还建立了该介体家族的生物合成途径，从而为控制巨噬细胞反应的机制提供了线索。
Macrophages are central in orchestrating the clearance of apoptotic cells and cellular debris during inflammation, with the mechanism(s) regulating this process remaining of interest. Herein, we found that the n-3 docosapentaenoic acid-derived protectin (PDn-3 DPA) biosynthetic pathway regulated the differentiation of human monocytes, altering macrophage phenotype, efferocytosis, and bacterial phagocytosis. Using lipid mediator profiling, human primary cells and recombinant enzymes we found that human 15-lipoxygenases initiate the PDn-3 DPA pathway catalyzing the formation of an allylic epoxide. The complete stereochemistry of this epoxide was determined using stereocontrolled total organic synthesis as 16S,17S-epoxy-7Z,10Z,12E,14E,19Z-docosapentaenoic acid (16S,17S-ePDn-3 DPA). This intermediate was enzymatically converted by epoxide hydrolases to PD1n-3 DPA and PD2n-3 DPA, with epoxide hydrolase 2 converting 16S,17S-ePDn-3 DPA to PD2n-3 DPA in human monocytes. Taken together these results establish the PDn-3 DPA biosynthetic pathway in human monocytes and macrophages and its role in regulating macrophage resolution responses. PDn-3 DPA regulates human monocyte-derived macrophage differentiation and function Evidence for the formation and complete stereochemistry of 16S,17S-ePDn-3 DPA EPHX2 converts 16S,17S-ePDn-3 DPA to PD2n-3 DPA in human monocytes Pistorius et al., found that a recently uncovered family of bioactive mediators termed PDn-3 DPA controls human macrophage phenotype and function during their differentiation from monocytes. The authors also established the biosynthetic pathway for this family of mediators thereby providing leads into mechanisms that control macrophage responses.
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DOI：
10.4049/jimmunol.1600837
发表时间：
2016-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Colas RA;Dalli J;Chiang N;Vlasakov I;Sanger JM;Riley IR;Serhan CN
通讯作者：
Serhan CN
DOI：
10.1074/jbc.m112.340612
发表时间：
2012-03-23
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Isobe Y;Arita M;Matsueda S;Iwamoto R;Fujihara T;Nakanishi H;Taguchi R;Masuda K;Sasaki K;Urabe D;Inoue M;Arai H
通讯作者：
Arai H
影响因子：
5.1
作者：
Aursnes M;Tungen JE;Colas RA;Vlasakov I;Dalli J;Serhan CN;Hansen TV
通讯作者：
Hansen TV
影响因子：
4.8
作者：
Pierdomenico, Anna Maria;Recchiuti, Antonio;Romano, Mario
通讯作者：
Romano, Mario
DOI：
10.1073/pnas.1206641109
发表时间：
2012-09-11
影响因子：
11.1
作者：
El Kebir, Driss;Gjorstrup, Per;Filep, Janos G.
通讯作者：
Filep, Janos G.