Enzymatic activity of ACE2 regulates type 2 airway inflammation in mice
Enzymatic activity of ACE2 regulates type 2 airway inflammation in mice
复制标题
ACE2 的酶活性调节小鼠 2 型气道炎症
作者：
Fukuda Asami;Toyoshima Shota;Yamada Shiho;Kurosawa Yusuke;Okayama Yoshimichi;Maruoka Shuichiro;Gon Yasuhiro
由新型严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已导致全球大流行。SARS-CoV-2刺突蛋白与血管紧张素转换酶2（ACE 2）结合，ACE 2是气道上皮表面宿主细胞上的一种跨膜内肽酶，用于侵袭和感染1;因此，大多数COVID-19研究都集中在ACE 2上。据报道，慢性阻塞性肺疾病和特发性肺纤维化患者的COVID-19发病率和死亡率都很高，2，3无论他们是否患有哮喘。哮喘是一种由环境因素引发的异质性疾病，如屋尘螨（HDM）和导致慢性气道炎症的病毒。5这些因素促进上皮细胞损伤，导致细胞因子的释放，引起2型（T2）炎症反应。6 Kimura等7报道，白细胞介素（IL）-13暴露可降低哮喘患者气道上皮中ACE 2的表达，而干扰素可增强ACE 2的表达。3，8 Camiolo et al 9还指出，ACE 2表达与病毒应答基因（如IFN和T细胞活化因子）的上调有关，在T2炎症-低哮喘患者亚组中，这些患者的特征对应于严重COVID-19的风险因素。总的来说，上皮细胞中ACE 2的低表达可能会保护哮喘患者免受COVID-19的影响。ACE 2不仅是SARS-CoV-2的受体，也是催化血管紧张素II转化为血管紧张素（1-7）的主要酶，在心血管疾病中发挥抗炎作用。10然而，哮喘相关的过敏性炎症和ACE 2酶活性之间的关系，而不是其在气道中的表达，尚未在体内评估。为了探索这些关联，我们使用了HDM诱导的哮喘小鼠模型，这是T2显性哮喘模型。在第0、7和14天，C57 BL/6 J小鼠肠道内暴露于或不暴露于HDM（10-15只小鼠/组）。在第3、10和17天采集支气管肺泡灌洗液（BALF）和肺组织样本，计数嗜酸性粒细胞并测量Ace 2表达（图1A，附录S1）。BALF样本中的嗜酸性粒细胞计数从第3天到第17天随着重复HDM暴露而逐步增加，
To the Editor, Coronavirus disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. SARS-CoV-2 spike protein binds to angiotensin-converting enzyme 2 (ACE2), a transmembrane endopeptidase on host cells of the airway epithelium surface for invasion and infection1; therefore, most COVID-19 research has focused on ACE2. Patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are reportedly at a high risk of COVID-19 morbidity and mortality, 2, 3 regardless of whether they have asthma. 4 Asthma is a heterogeneous disease triggered by environmental factors such as house dust mites (HDM) and viruses that cause chronic airway inflammation. 5 These factors promote epithelial cell damage, leading to the release of cytokines that provoke a type 2 (T2) inflammatory response. 6 Kimura et al7 reported that interleukin (IL)-13 exposure reduces ACE2 expression in the airway epithelium of patients with asthma, whereas interferons enhance ACE2 expression. 3, 8 Camiolo et al9 also indicated that ACE2 expression is linked to up-regulation of viral response genes, such as IFNs and T-cell-activating factors, in a subset of patients with T2 inflammation-low asthma with characteristics corresponding to risk factors for severe COVID-19. Overall, low ACE2 expression in epithelial cells may protect patients with asthma from COVID-19. ACE2 is not only a receptor for SARS-CoV-2 but also the main enzyme for catalyzing the conversion of angiotensin II into angiotensin (1–7) and exerts anti-inflammatory effects in cardiovascular diseases. 10 However, the relationship between asthma-related allergic inflammation and ACE2 enzymatic activity, but not its expression in the airway, has not been assessed in vivo. To explore these associations, we used an HDM-induced asthma mouse model, which is T2 dominant asthma model. C57BL/6 J mice were intratracheally exposed or not to HDM (10–15 mice/group) at days 0, 7, and 14. Bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested at days 3, 10, and 17 to count eosinophils and measure Ace2 expression (Figure 1A, Appendix S1). The eosinophil counts in BALF samples increased from day 3 to 17 concomitantly with repeated HDM exposure in a stepwise