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ангиотензин转化酶的古典和非古典效应:增加的 ACE 如何增强骨髓细胞免疫功能

Kenneth E Bernstein¹, DuoYao Cao², Tomohiro Shibata³

¹Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.

The Journal of biological chemistry

|May 19, 2024

概括

ангиотензин转化酶 (ACE) 在免疫细胞中具有非经典的作用,促进新陈代谢和抗病能力. 准这种未知的ACE激活分子可能会提供新的治疗途径.

科学领域:

免疫学免疫学免疫学
生物化学生物化学
代谢医学是一种代谢医学.

背景情况:

氨酸- ангиотензин系统通常涉及 ангиотензин转化酶 (ACE),产生 ангиотензин II,影响心血管功能,炎症和增殖.
ACE还表现出非经典的功能,由巨细胞和中性粒细胞等免疫细胞产生的,影响髓状细胞活动,独立于血管新生II.

研究的目的:

探索ACE在免疫细胞中的非经典功能及其治疗潜力.
研究骨髓状细胞中ACE表达增加的代谢和功能后果.

主要方法:

使用了基因改造的小鼠模型 (ACE 10/10和NeuACE),分别在巨细胞和中性粒细胞中增强了ACE表达.
评估疾病耐药性 (瘤,感染,动脉样硬化,阿尔茨海默氏症) 和髓状细胞代谢 (氧化代谢,ATP水平,PPARα表达).
研究了ACE在精子功能和受精中的作用.

主要成果:

增加巨细胞ACE (ACE 10/10) 的小鼠对瘤,感染,动脉样硬化和阿尔茨海默病模型表现出抵抗力.
增加中性粒细胞ACE (NeuACE) 的小鼠对感染更具抵抗力;ACE抑制剂降低了细菌的杀死.
增强的ACE表达增加了巨细胞的氧化代谢,脂质氧化和ATP水平,与PPARα上调相关.

结论:

非经典的ACE功能,独立于血管新生素II,通过未知的介质深刻改变髓状细胞的新陈代谢和功能.
针对这种新型的ACE介导途径,为各种疾病提供了潜在的治疗策略.
对这种的进一步研究可能会导致有利可图的治疗选择.

关键词:

阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.ангиотензин II 的使用血管氨酸转化酶 - 血管氨酸转化酶动脉样硬化动脉样硬化癌症癌症癌症癌症癌症免疫学免疫学免疫学传染病是一种传染性疾病.巨细胞是一个巨细胞.作为一个中性恋者.

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