In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS
In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS
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DOI：
10.1096/fj.02-0331com
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发表时间：
2002-11-01
期刊：
影响因子：
4.8
通讯作者：
Mason, RP
中科院分区：
文献类型：
--
作者：
Sato, K;Kadiiska, MB;Mason, RP
气管内滴注脂多糖（LPS）会激活肺泡巨噬细胞和中性粒细胞浸润，引起肺损伤/急性呼吸窘迫综合征。自由基作为 LPS 引起的肺损伤发病机制中的最终致病分子而受到特别关注。尽管体外研究已证明细胞暴露于 LPS 后会产生自由基，但体内证据仍缺乏。利用电子自旋共振 (ESR) 和自旋陷阱 α-(4-吡啶基-1-氧化物)-N-叔丁基硝酮 (POBN)，我们研究了经气管内滴注 LPS 治疗的大鼠体内自由基的产生。暴露于 LPS 6 小时的肺部脂质提取物的 ESR 光谱得出的光谱与 POBN/碳中心自由基加合物 (a(N) =14.94+/-0.07 G 和 a(beta)(H)=2.42+/-0.06 G）的光谱一致，暂定为脂质过氧化产物。为了进一步研究 LPS 引发自由基产生的机制，用吞噬细胞毒物 GdCl3 预处理大鼠，显着减少自由基加合物的产生，并相应减少中性粒细胞浸润。在这种急性肺损伤模型中，NADPH 氧化酶敲除小鼠完全阻断了吞噬细胞介导的、ESR 可检测到的自由基产生。气管内注射 LPS 的大鼠通过激活 NADPH 氧化酶产生脂质衍生的自由基。
Intratracheal instillation of lipopolysaccharide (LPS) activates alveolar macrophages and infiltration of neutrophils, causing lung injury/acute respiratory distress syndrome. Free radicals are a special focus as the final causative molecules in the pathogenesis of lung injury caused by LPS. Although in vitro investigation has demonstrated radical generation after exposure of cells to LPS, in vivo evidence is lacking. Using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we investigated in vivo free radical production by rats treated with intratracheal instillation of LPS. ESR spectroscopy of lipid extract from lungs exposed to LPS for 6 h gave a spectrum consistent with that of a POBN/carbon-centered radical adduct (a(N) =14.94+/-0.07 G and a(beta)(H)=2.42+/-0.06 G) tentatively assigned as a product of lipid peroxidation. To further investigate the mechanism of LPS-initiated free radical generation, rats were pretreated with the phagocytic toxicant GdCl3, which significantly decreased the production of radical adducts with a corresponding decrease in neutrophil infiltration. NADPH oxidase knockout mice completely blocked phagocyte-mediated, ESR-detectable radical production in this model of acute lung injury. Rats treated intratracheally with LPS generate lipid-derived free radicals via activation of NADPH oxidase.