Angiotensin-converting enzyme enhances the oxidative response and bactericidal activity of neutrophils
Angiotensin-converting enzyme enhances the oxidative response and bactericidal activity of neutrophils
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DOI：
10.1182/blood-2016-11-752006
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发表时间：
2017-07-20
期刊：
影响因子：
20.3
通讯作者：
Bernstein, Kenneth E.
中科院分区：
文献类型：
--
作者：
Khan, Zakir;Shen, Xiao Z.;Bernstein, Kenneth E.
血管紧张素转换酶（ACE）抑制剂被广泛用于降低血压。在这里，我们研究了ACE是否对中性粒细胞的抗菌效果很重要。ACE基因敲除小鼠或ACE抑制剂治疗小鼠对耐甲氧西林金黄色葡萄球菌（MRSA）的细菌感染更敏感。相比之下，在中性粒细胞中过表达ACE的小鼠（Neu（ACE）小鼠）对MRSA的抗性增加，并且对MRSA、铜绿假单胞菌和肺炎克雷伯菌的体外杀灭效果更好。ACE过表达增加了MRSA感染后中性粒细胞活性氧（ROS）的产生，这种作用不依赖于血管紧张素II AT1受体。特别是，与野生型（WT）小鼠相比，超氧化物生成显著增加（> 2倍，P
Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if an ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant Staphylococcus aureus (MRSA). In contrast, mice overexpressing ACE in neutrophils (Neu(ACE) mice) have increased resistance to MRSA and better in vitro killing of MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae. ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor. Specifically, as compared with wild-type (WT) mice, there was a marked increase of superoxide generation (>twofold, P