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Role of angiotensin-converting enzyme in myeloid cell immune responses.
Cellular & Molecular Biology Letters ( IF 9.2 ) Pub Date : 2020-05-25 , DOI: 10.1186/s11658-020-00225-w
Duo-Yao Cao 1 , Suguru Saito 1 , Luciana C Veiras 1 , Derick Okwan-Duodu 1, 2 , Ellen A Bernstein 1 , Jorge F Giani 1, 2 , Kenneth E Bernstein 1, 2 , Zakir Khan 1, 2
Affiliation  

Angiotensin-converting enzyme (ACE), a dicarboxypeptidase, plays a major role in the regulation of blood pressure by cleaving angiotensin I into angiotensin II (Ang II), a potent vasoconstrictor. Because of its wide substrate specificity and tissue distribution, ACE affects many diverse biological processes. In inflammatory diseases, including granuloma, atherosclerosis, chronic kidney disease and bacterial infection, ACE expression gets upregulated in immune cells, especially in myeloid cells. With increasing evidences connecting ACE functions to the pathogenesis of these acquired diseases, it is suggested that ACE plays a vital role in immune functions. Recent studies with mouse models of bacterial infection and tumor suggest that ACE plays an important role in the immune responses of myeloid cells. Inhibition of ACE suppresses neutrophil immune response to bacterial infection. In contrast, ACE overexpression in myeloid cells strongly induced bacterial and tumor resistance in mice. A detailed biochemical understanding of how ACE activates myeloid cells and which ACE peptide(s) (substrate or product) mediate these effects could lead to the development of novel therapies for boosting immunity against a variety of stimuli, including bacterial infection and tumor.

中文翻译:

血管紧张素转换酶在髓样细胞免疫反应中的作用。

血管紧张素转换酶(ACE)是一种二羧基肽酶,通过将血管紧张素I裂解为血管紧张素II(Ang II)(一种有效的血管收缩剂),在血压调节中起主要作用。由于其广泛的底物特异性和组织分布,ACE影响许多不同的生物学过程。在包括肉芽肿,动脉粥样硬化,慢性肾脏疾病和细菌感染在内的炎性疾病中,ACE表达在免疫细胞(尤其是骨髓细胞)中上调。越来越多的证据将ACE功能与这些获得性疾病的发病机制联系起来,这表明ACE在免疫功能中起着至关重要的作用。小鼠细菌感染和肿瘤模型的最新研究表明,ACE在髓样细胞的免疫反应中起着重要作用。ACE的抑制抑制中性粒细胞对细菌感染的免疫反应。相反,ACE在髓样细胞中的过表达强烈诱导了小鼠的细菌和肿瘤抗性。对ACE如何激活髓样细胞以及哪种ACE肽(底物或产物)介导这些作用的详细生化理解可能会导致开发出新的疗法,以增强针对各种刺激的免疫力,包括细菌感染和肿瘤。
更新日期:2020-07-24
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