期刊
CELL CHEMICAL BIOLOGY
卷 25, 期 6, 页码 749-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2018.04.017
关键词
-
资金
- School of Pharmacy, University of Oslo
- Norwegian Research Council [FRIPRO/FRINATEK 230470]
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [677542]
- Barts Charity [MGU0343]
- Sir Henry Dale Fellowship - Wellcome Trust
- Sir Henry Dale Fellowship - Royal Society [107613/Z/15/Z]
- Wellcome Trust Infrastructure [101604/Z/13/Z]
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 phagocy-tosis. 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-ePD(n-3 DPA)). This intermediate was enzymatically converted by epoxide hydrolases to PD1(n-3 DPA) and PD2(n-3 DPA), with epoxide hydrolase 2 converting 16S,17S-ePD(n-3) (DPA) to PD2(n-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据