An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo.
An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo.
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DOI：
10.1126/scitranslmed.abj2138
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发表时间：
2021-07-28
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
--
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血管紧张素转换酶抑制剂（ACEIs）被数百万患者用于治疗高血压、糖尿病肾病和心力衰竭。然而，这些患者往往感染的风险增加。为了评估ACEI对感染免疫应答的影响，我们比较了ACEI与血管紧张素受体阻滞剂（ARB）对中性粒细胞抗菌活性的影响。ACEI暴露降低了小鼠中性粒细胞体外杀死耐甲氧西林金黄色葡萄球菌（MRSA）、铜绿假单胞菌和肺炎克雷伯菌的能力。在体内，与ARB或无药物治疗的小鼠相比，感染MRSA的ACEI治疗小鼠的菌血症和组织细菌计数增加。同样，ACEI，而不是ARB，增加了主动脉瓣损伤小鼠MRSA诱导的感染性心内膜炎的发病率。来自ACE敲除（KO）小鼠或ACEI治疗小鼠的中性粒细胞在MRSA或脂多糖刺激后产生较少的白三烯B4（LTB4），而与野生型中性粒细胞相比，过表达ACE的中性粒细胞产生更多的LTB4。作为LTB4产生减少的结果，ACE KO中性粒细胞显示存活信号降低和凋亡增加。相反，中性粒细胞过度表达ACE有增强的生存表型。最后，在接受ACEI雷米普利1周的志愿者队列中，ACEI给药减少了中性粒细胞超氧化物和活性氧的产生，并且雷米普利治疗期间从志愿者中分离的中性粒细胞的杀菌活性降低。总之，这些数据表明，ACEI治疗，而不是ARB治疗，可以降低嗜中性粒细胞的细菌杀伤能力。
Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these patients are often at increased risk of infection. To evaluate the impact of ACEIs on immune responses to infection, we compared the effect of an ACEI versus an angiotensin receptor blocker (ARB) on neutrophil antibacterial activity. ACEI exposure reduced the ability of murine neutrophils to kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae in vitro. In vivo, ACEI-treated mice infected with MRSA had increased bacteremia and tissue bacteria counts compared to mice treated with an ARB or with no drug. Similarly, ACEIs, but not ARBs, increased the incidence of MRSA-induced infective endocarditis in mice with aortic valve injury. Neutrophils from ACE knockout (KO) mice or mice treated with an ACEI produced less leukotriene B4 (LTB4) upon stimulation with MRSA or lipopolysaccharide, whereas neutrophils overexpressing ACE produced more LTB4 compared to wild-type neutrophils. As a result of reduced LTB4 production, ACE KO neutrophils showed decreased survival signaling and increased apoptosis. In contrast, neutrophils overexpressing ACE had an enhanced survival phenotype. Last, in a cohort of human volunteers receiving the ACEI ramipril for 1 week, ACEI administration reduced neutrophil superoxide and reactive oxygen species production and neutrophils isolated from volunteers during ramipril treatment had reduced bactericidal activity. Together, these data demonstrate that ACEI treatment, but not ARB treatment, can reduce the bacterial killing ability of neutrophils.
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影响因子：
20.3
作者：
Khan, Zakir;Shen, Xiao Z.;Bernstein, Kenneth E.
通讯作者：
Bernstein, Kenneth E.
炎性关节炎需要中性粒细胞的白细胞B4。
DOI：
10.1084/jem.20052371
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
2.6
作者：
Danilov, SM;Sadovnikova, E;Adema, GJ
通讯作者：
Adema, GJ
影响因子：
4.8
作者：
Cao, Duo-Yao;Spivia, Weston R.;Bernstein, Kenneth E.
通讯作者：
Bernstein, Kenneth E.
影响因子：
15.9
作者：
Dang, Pham My-Chan;Stensballe, Allan;El-Benna, Jamel
通讯作者：
El-Benna, Jamel