Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.
Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.
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DOI：
10.1016/j.cell.2008.02.043
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发表时间：
2008-04-18
期刊：
影响因子：
64.5
通讯作者：
Penninger JM
中科院分区：
文献类型：
--
作者：
Imai Y;Kuba K;Neely GG;Yaghubian-Malhami R;Perkmann T;van Loo G;Ermolaeva M;Veldhuizen R;Leung YH;Wang H;Liu H;Sun Y;Pasparakis M;Kopf M;Mech C;Bavari S;Peiris JS;Slutsky AS;Akira S;Hultqvist M;Holmdahl R;Nicholls J;Jiang C;Binder CJ;Penninger JM
多种肺部病原体，如化学制剂、H5N1禽流感或SARS，由于急性呼吸窘迫综合征而导致高致死率。在此，我们报道了Toll样受体4(TLR4)突变小鼠对酸诱导的急性肺损伤(ALI)表现出天然的抵抗力。我们认为TLR4-TRIF-TRAF6信号通路是控制ALI严重程度的关键疾病通路。氧化磷脂(OxPL)OxPAPC可通过TLR4-TRIF诱导肺损伤和肺巨噬细胞产生细胞因子。我们观察了感染SARS、炭疽或H5N1的人和动物肺中OxPL的产生。用灭活的H5N1禽流感病毒肺攻击小鼠可迅速诱导ALI和OxPL的形成。TLR4或TRIF表达的缺失对H5N1诱导的ALI小鼠具有保护作用。此外，控制ROS产生的ncf1的缺失提高了H5N1介导的ALI的严重性。我们的数据表明，氧化应激和先天免疫是控制ALI严重程度的关键肺损伤途径。
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
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DOI：
10.1084/jem.20031763
发表时间：
2004-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chang MK;Binder CJ;Miller YI;Subbanagounder G;Silverman GJ;Berliner JA;Witztum JL
通讯作者：
Witztum JL
影响因子：
4.4
作者：
Knapp, Sylvia;Matt, Ulrich;van der Poll, Tom
通讯作者：
van der Poll, Tom
影响因子：
64.8
作者：
Kobasa, D;Takada, A;Kawaoka, Y
通讯作者：
Kawaoka, Y
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
6.4
作者：
Haeberle, HA;Takizawa, R;Garofalo, RP
通讯作者：
Garofalo, RP