Fatty acid ethyl esters disrupt neonatal alveolar macrophage mitochondria and derange cellular functioning.
Fatty acid ethyl esters disrupt neonatal alveolar macrophage mitochondria and derange cellular functioning.
复制标题
脂肪酸乙酯会破坏新生儿肺泡巨噬细胞线粒体并扰乱细胞功能。
DOI：
10.1111/acer.12647
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Gauthier,TheresaW
中科院分区：
文献类型：
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作者：
Mohan,SowmyaS;Ping,XiaoDu;Harris,FrankL;Ronda,NecolJ;Brown,LouAnnS;Gauthier,TheresaW
背景：慢性酒精暴露会改变肺泡巨噬细胞（AM）的功能，损害成人和新生儿肺部的免疫防御。脂肪酸乙酯（FAEEs）是新生儿产前酒精暴露的生物学标志物。FAEEs有助于酒精诱导的多器官线粒体（MT）损伤。我们假设在子宫内乙醇暴露会增加新生儿肺部的FAEEs，而新生儿AM直接暴露于FAEEs会导致MT损伤和细胞功能障碍。方法采用气相色谱/质谱联用法测定胎内乙醇暴露后新生豚鼠肺中faes的含量。将NR8383细胞系和新分离的新生豚鼠AM体外暴露于油酸乙酯（EO）中。在暴露于EO±MT特异性抗氧化剂mito - TEMPO （mitoT）或±pan - caspase抑制剂Z - VAD - FMK后，评估MT膜电位、MT活性氧生成（mROS）、吞噬和凋亡。采用Mann-WhitneyU‐检验比较全肺fae。细胞结果采用单因素方差分析进行分析，随后采用Student-Newman-Keuls方法进行事后比较。结果子宫内乙醇显著增加了新生儿肺中亚油酸乙酯、亚油酸乙酯+亚油酸+亚麻酸酯（OLL）、OLL +硬脂酸酯。体外EO对NR8383和原发性新生儿AM均造成明显的MT功能障碍，这可以通过mROS增加和MT膜电位丧失来证明。暴露于EO后，细胞系和原代AM的吞噬功能受损和凋亡明显增加。MitoT对EO诱导的MT损伤具有显著但仅部分的保护作用，Z - VAD - FMK对caspase的抑制也具有同样的作用。结论子宫内乙醇暴露增加了新生豚鼠肺FAEEs。直接暴露于FAEE EO显著导致AM功能障碍，部分是通过对MT的氧化损伤，部分是通过继发性细胞凋亡。
BackgroundChronic alcohol exposure alters the function of alveolar macrophages (AM), impairing immune defenses in both adult and neonatal lungs. Fatty acid ethyl esters (FAEEs) are biological markers of prenatal alcohol exposure in newborns. FAEEs contribute to alcohol‐induced mitochondrial (MT) damage in multiple organs. We hypothesized that in utero ethanol exposure would increase FAEEs in the neonatal lung and that direct exposure of neonatal AM to FAEEs would contribute to MT injury and cellular dysfunction.MethodsFAEEs were measured in neonatal guinea pig lungs after ± in utero ethanol exposure via gas chromatography/mass spectrometry. The NR8383 cell line and freshly isolated neonatal guinea pig AM were exposed to ethyl oleate (EO) in vitro. MT membrane potential, MT reactive oxygen species generation (mROS), phagocytosis, and apoptosis were evaluated after exposure to EO ± the MT‐specific antioxidant mito‐TEMPO (mitoT) or ± the pan‐caspase inhibitor Z‐VAD‐FMK. Whole lung FAEEs were compared using the Mann–WhitneyU‐test. Cellular results were analyzed using 1‐way analysis of variance, followed by the Student–Newman–Keuls Method for post hoc comparisons.ResultsIn utero ethanol significantly increased ethyl linoleate and the combinations of ethyl oleate + linoleate + linolenate (OLL), and OLL + stearate in the neonatal lung. In vitro EO caused significant MT dysfunction in both NR8383 and primary neonatal AM, as indicated by increased mROS and loss of MT membrane potential. Impaired phagocytosis and apoptosis were significantly increased in both the cell line and primary AM after EO exposure. MitoT conferred significant but only partial protection against EO‐induced MT injury, as did caspase inhibition with Z‐VAD‐FMK.ConclusionsIn utero ethanol exposure increased FAEEs in the neonatal guinea pig lung. Direct exposure to the FAEE EO significantly contributed to AM dysfunction, in part via oxidant injury to the MT and in part via secondary apoptosis.