Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation.

Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation.
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DOI:
10.4049/jimmunol.1600837
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发表时间:
2016-12-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Serhan CN
Serhan CN
中科院分区:
其他
文献类型:
--
作者:
Colas RA;Dalli J;Chiang N;Vlasakov I;Sanger JM;Riley IR;Serhan CN

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Maresin 1(MaR 1)是一种免疫溶解剂,控制急性炎症的消退,其在感染性炎症背景下的局部代谢是令人感兴趣的。在这里,我们研究了MaR 1代谢组在感染性渗出液和它的生物作用,在细菌感染的背景下调节白细胞反应。在大肠杆菌感染性渗出液中,MaR 1在4 h时达到最大水平(2.2 ± 0.4 pg/灌洗液)。在这些渗出物中,我们还鉴定了两种新的产物,并对其结构进行了解析,得到了22-羟基-MaR 1和14-氧代-MaR 1。使用人原代白细胞,我们发现中性粒细胞主要产生22-OH-MaR 1,而主要的巨噬细胞产物是14-oxo-MaR 1。与人原代巨噬细胞一起孵育的22-OH-MaR 1和14-oxo-MaR 1在1 pM 22-OH-MaR 1和1 pM 14-oxo-MaR 1下均使巨噬细胞吞噬作用剂量依赖性增加约75%,而14-oxo-MaR 1在较高浓度下的活性低于MaR 1。这些发现共同建立了感染性炎症期间MaR 1的时间调节,并阐明了两种新的MaR 1进一步代谢产物的结构和作用。
Maresin 1 (MaR1) is an immunoresolvent that governs resolution of acute inflammation and its local metabolism in the context infectious-inflammation is of interest. Here, we investigated the MaR1 metabolome in infectious exudates and its bioactions in regulating leukocyte responses in the context of bacterial infection. In Escherichia coli infectious exudates, MaR1 was temporally regulated with maximal levels at 4 h (2.2 ± 0.4 pg/lavage). In these exudates we also identified two novel products and their structure elucidation gave 22-hydroxy-MaR1 and 14-oxo-MaR1. Using human primary leukocytes we found that neutrophils primarily produced 22-OH-MaR1 whereas the main macrophage product was 14-oxo-MaR1. Both 22-OH-MaR1 and 14-oxo-MaR1 incubated with human primary macrophages gave dose dependent increases in macrophage phagocytosis of ~75% at 1 pM 22-OH-MaR1 and ~25% at 1 pM 14-oxo-MaR1, while 14-oxo-MaR1 was less active than MaR1 at higher concentrations. Together these findings establish the temporal regulation of MaR1 during infectious inflammation as well as elucidate the structures and actions of two novel MaR1 further metabolites that carry bioactivities.
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