Identification and Actions of a Novel Third Maresin Conjugate in Tissue Regeneration: MCTR3.
Identification and Actions of a Novel Third Maresin Conjugate in Tissue Regeneration: MCTR3.
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新型第三Maresin结合物在组织再生中的鉴定和作用：MCTR3。
DOI：
10.1371/journal.pone.0149319
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Serhan CN
中科院分区：
文献类型：
--
作者：
Dalli J;Sanger JM;Rodriguez AR;Chiang N;Spur BW;Serhan CN
Maresin conjugates in tissue regeneration （MCTR）是一类新的进化上保守的化学信号，可协调宿主反应，促进组织再生和感染的解决。在此，我们鉴定了新的MCTR3，建立了等级效价，并使用全有机合成制备的材料和从小鼠和人系统中分离的介质匹配了MCTR1， MCTR2和MCTR3的立体化学。MCTR3由内源性底物由大肠杆菌激活的人巨噬细胞产生，并在脓毒症患者中被鉴定。三种合成MCTR均呈剂量依赖性（1-100nM），可加速涡虫组织再生0.6-0.9天。当在炎症开始或高峰期给药时，每一种MCTR都促进了小鼠大肠杆菌感染的消退。它们通过渗出白细胞增加细菌吞噬（~ 15-50%），限制中性粒细胞浸润（~ 20-50%），促进efferocysis（~30%）和减少二十烷类蛋白。MCTR1和MCTR2上调人中性粒细胞和巨噬细胞的吞噬反应，其中MCTR3也被证明具有有效的作用。这些结果建立了MCTR1， MCTR2和MCTR3的完整立体化学和秩序效力，为调节宿主对清除感染的反应和促进组织再生提供了新的分辨率模块。
Maresin conjugates in tissue regeneration (MCTR) are a new family of evolutionarily conserved chemical signals that orchestrate host responses to promote tissue regeneration and resolution of infections. Herein, we identified the novel MCTR3 and established rank order potencies and matched the stereochemistries of MCTR1, MCTR2 and MCTR3 using material prepared by total organic synthesis and mediators isolated from both mouse and human systems. MCTR3 was produced from endogenous substrate by E. coli activated human macrophages and identified in sepsis patients. Each of the three synthetic MCTR dose-dependently (1–100nM) accelerated tissue regeneration in planaria by 0.6–0.9 days. When administered at the onset or peak of inflammation, each of the MCTR promoted resolution of E. coli infections in mice. They increased bacterial phagocytosis by exudate leukocytes (~15–50%), limited neutrophil infiltration (~20–50%), promoted efferocytosis (~30%) and reduced eicosanoids. MCTR1 and MCTR2 upregulated human neutrophil and macrophage phagocytic responses where MCTR3 also proved to possess potent actions. These results establish the complete stereochemistry and rank order potencies for MCTR1, MCTR2 and MCTR3 that provide novel resolution moduli in regulating host responses to clear infections and promote tissue regeneration.