Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation.
Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation.
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阿司匹林触发的溶质D1是在自由分辨的革兰氏阴性细菌性肺炎过程中产生的，并调节宿主免疫反应以解决肺部炎症。
作者：
细菌性肺炎是全世界发病率和死亡率的主要原因。宿主对控制感染和减轻病原体介导的肺部炎症的反应对肺炎的解决至关重要。阿司匹林触发的解决素D_1(AT-RvD_1；7S，8R，17R三羟基-4Z，9E，11E，13Z，15E，19Z二十二碳六烯酸)是一种脂质介质，在无菌肺部炎症中发挥器官保护作用，并调节病原体启动的细胞反应。在自行解决的大肠杆菌肺炎小鼠模型中，在基线、感染后24小时和72小时对肺进行的脂质介体代谢脂组学研究揭示了内源性AT-RvD1产生的时间调节。早期使用外源性AT-RvD1(感染后1小时)可增强体内对大肠杆菌和铜绿假单胞菌的清除，以及体外对肺巨噬细胞吞噬荧光细菌颗粒的作用。肺炎期间肺泡室巨噬细胞亚群的特征确定了通过渗入巨噬细胞(CD11bHi CD11cLow)和渗出性巨噬细胞(CD11bHi CD11cHi)产生的吞噬作用。AT-RvD1在体外增加了这些细胞的胞吐作用，并在体内加速了肺炎期间中性粒细胞的清除。AT-RvD1的这些抗菌和促分解作用是抗生素治疗的补充。综上所述，这些发现表明，AT-RvD1在肺炎期间的促分解作用代表了一种新的宿主指导的治疗策略，以补充目前以抗生素为中心的对抗感染的方法。
Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Host responses to contain infection and mitigate pathogen-mediated lung inflammation are critical for pneumonia resolution. Aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R trihydroxy-4Z,9E,11E,13Z,15E,19Z docosahexaenoic acid) is a lipid mediator that displays organ protective actions in sterile lung inflammation, and regulates pathogen-initiated cellular responses. Here, in a self-resolving murine model of Escherichia coli pneumonia, lipid mediator metabololipidomics performed on lungs obtained at baseline, 24 hours and 72 hours after infection uncovered temporal regulation of endogenous AT-RvD1 production. Early treatment with exogenous AT-RvD1 (1 hr post-infection) enhanced clearance of E.coli and Pseudomonas aeruginosa in vivo, and lung macrophage phagocytosis of fluorescent bacterial particles ex vivo. Characterization of macrophage subsets in the alveolar compartment during pneumonia identified efferocytosis by infiltrating macrophages (CD11bHi CD11cLow) and exudative macrophages (CD11bHi CD11cHi). AT-RvD1 increased efferocytosis by these cells ex vivo, and accelerated neutrophil clearance during pneumonia in vivo. These anti-bacterial and pro-resolving actions of AT-RvD1 were additive to antibiotic therapy. Taken together, these findings suggest that the pro-resolving actions of AT-RvD1 during pneumonia represent a novel host-directed therapeutic strategy to complement the current antibiotic centered approach to combatting infections.
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DOI：
10.1056/nejmra0904124
发表时间：
2010-05-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Peleg AY;Hooper DC
通讯作者：
Hooper DC
影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
淋巴组织磷脂酶A2组IID通过驱动抗炎脂质介质来解决接触性超敏反应。
DOI：
10.1084/jem.20121887
发表时间：
2013-06-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Miki Y;Yamamoto K;Taketomi Y;Sato H;Shimo K;Kobayashi T;Ishikawa Y;Ishii T;Nakanishi H;Ikeda K;Taguchi R;Kabashima K;Arita M;Arai H;Lambeau G;Bollinger JM;Hara S;Gelb MH;Murakami M
通讯作者：
Murakami M
DOI：
10.4049/jimmunol.1300699
发表时间：
2013-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Divanovic S;Dalli J;Jorge-Nebert LF;Flick LM;Gálvez-Peralta M;Boespflug ND;Stankiewicz TE;Fitzgerald JM;Somarathna M;Karp CL;Serhan CN;Nebert DW
通讯作者：
Nebert DW
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.