Colas Romain A, Dalli Jesmond, Chiang Nan, Vlasakov Iliyan, Sanger Julia M, Riley Ian R, Serhan Charles N
Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
J Immunol. 2016 Dec 1;197(11):4444-4452. doi: 10.4049/jimmunol.1600837. Epub 2016 Oct 31.
Maresin 1 (MaR1) is an immunoresolvent that governs resolution of acute inflammation, and its local metabolism in the context of infectious inflammation is of interest. In this study, 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, whereas 14-oxo-MaR1 was less active than MaR1 at higher concentrations. Together these findings establish the temporal regulation of MaR1 during infectious inflammation, and elucidate the structures and actions of two novel MaR1 further metabolites that carry bioactivities.
maresin 1（MaR1）是一种免疫溶解介质，可控制急性炎症的消退，其在感染性炎症背景下的局部代谢备受关注。在本研究中，我们调查了感染性渗出物中的MaR1代谢组及其在细菌感染背景下调节白细胞反应的生物活性。在大肠杆菌感染性渗出物中，MaR1呈时间依赖性调节，4小时时达到最高水平（2.2±0.4 pg/灌洗）。在这些渗出物中，我们还鉴定出两种新产物，其结构解析确定为22-羟基-MaR1和14-氧代-MaR1。使用人原代白细胞，我们发现中性粒细胞主要产生22-OH-MaR1，而巨噬细胞的主要产物是14-氧代-MaR1。将22-OH-MaR1和14-氧代-MaR1与人原代巨噬细胞一起孵育，在1 pM 22-OH-MaR1时巨噬细胞吞噬作用剂量依赖性增加约75%，在1 pM 14-氧代-MaR1时增加约25%，而在较高浓度下14-氧代-MaR1的活性低于MaR1。这些发现共同确立了感染性炎症期间MaR1的时间调节，并阐明了两种具有生物活性的新型MaR1进一步代谢产物的结构和作用。
