Expression of neutral endopeptidase activity during clinical and experimental acute lung injury.
Expression of neutral endopeptidase activity during clinical and experimental acute lung injury.
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DOI：
10.1186/1465-9921-11-164
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发表时间：
2010-11-29
影响因子：
5.8
通讯作者：
Hashimoto S
中科院分区：
文献类型：
--
作者：
Hashimoto S;Amaya F;Oh-Hashi K;Kiuchi K;Hashimoto S
中性内肽酶（NEP）是一种裂解炎性生物活性肽的酶，在急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）的发病机制中可能起保护作用。然而，其低的细胞外活性阻碍了在ALI/ARDS期间发生的变化的精确测量。本研究的主要目的是阐明NEP活性及其表达在ALI/ARDS中的调节。在一项临床研究中，我们使用HPLC荧光系统测定了术后发生ALI/ARDS患者的血浆NEP活性。在一项实验研究中，我们通过在小鼠体内注入盐酸（HCl）或脂多糖（LPS）诱导ALI，并类似地测量血浆、肺组织和支气管肺泡灌洗液（BALF）中的NEP活性。我们还研究了分布，并测量NEP蛋白的量，使用免疫组织化学和免疫印迹分析，并测量NEP mRNA的水平，使用实时逆转录-聚合酶链反应，在肺与ALI小鼠。ALI/ARDS患者血浆NEP活性明显低于对照组。同样，血浆和肺组织中的NEP活性显着降低，肺损伤更严重的LPS-比盐酸治疗的小鼠。与此相反，LPS处理的小鼠BALF中的NEP活性增加。肺内灌注LPS可降低肺组织NEP基因表达。小鼠免疫组织化学和Western免疫印迹研究证实：a）NEP存在于肺泡壁中，这是ALI/ARDS的关键靶点;和B）NEP在HCl和LPS诱导的ALI中的表达降低。在本实验和临床研究中发现，ALI/ARDS时血浆NEP活性明显降低，肺泡气腔NEP活性明显升高。
Neutral endopeptidase (NEP), an enzyme that cleaves inflammatory bioactive peptides, may play a protective role in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, its low extracellular activity hinders the precise measurement of changes that take place during ALI/ARDS. The main objective of this study was to clarify the regulation of NEP activity and its expression during ALI/ARDS. In a clinical study, we measured plasma NEP activity in patients who developed postoperative ALI/ARDS, using a HPLC fluorometric system. In an experimental study, we induced ALI by intratracheal instillation of hydrochloric acid (HCl) or lipopolysaccharide (LPS) in mice, and similarly measured NEP activity in plasma, lung tissue, and broncho-alveolar lavage fluid (BALF). We also studied the distribution and measured the amounts of NEP protein, using immuno-histochemical and immunoblot analyses, and measured the levels of NEP mRNA, using real-time reverse transcription-polymerase chain reaction, in the lungs of mice with ALI. The plasma NEP activity was significantly lower in patients presenting with ALI/ARDS than in controls. Similarly, the NEP activity in plasma and lung tissue was markedly lower, and lung injuries more severe in LPS- than in HCl-treated mice. In contrast, the activity of NEP in the BALF of LPS-treated mice was increased. The intratracheal instillation of LPS decreased the gene expression of NEP in the lung. Immuno-histochemical and Western immunoblot studies in mice confirmed a) the presence of NEP in the alveolar wall, a critical target in ALI/ARDS, and b) a decrease in its expression in HCl- and LPS-induced ALI. In this experimental and clinical study of ALI/ARDS, the activity of NEP was significantly decreased in plasma and increased in the alveolar air space.
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影响因子：
3.2
作者：
Jacob S;Deyo DJ;Cox RA;Traber DL;Herndon DN;Hawkins HK
通讯作者：
Hawkins HK
影响因子：
4.8
作者：
Leissring, MA;Lu, A;Selkoe, DJ
通讯作者：
Selkoe, DJ
影响因子：
4.8
作者：
Clapéron, A;Rose, C;Ouimet, T
通讯作者：
Ouimet, T
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
3.3
作者：
Imai, Y;Nakagawa, S;Miyasaka, K
通讯作者：
Miyasaka, K