Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea; Sensory Organ Research Institute, Seoul National University Medical Research Center.
Rhinology. 2021 Oct 1;59(5):460-469. doi: 10.4193/Rhin21.001.
Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype.
ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP).
In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP.
ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.
血管紧张素转换酶 2（ACE2）是严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的靶标受体，在鼻黏膜中高度表达。慢性鼻-鼻窦炎（CRS）表现出多种表型，并且会加重病毒感染。病毒刺激和 CRS 表型是否会影响 ACE2 的表达尚不清楚。我们研究了 ACE2 和跨膜丝氨酸蛋白酶 2（TMPRSS2）的表达，SARS-CoV-2 通过这两种蛋白进入细胞，并且根据 CRS 表型评估多聚肌苷酸：多聚胞苷酸（poly[I:C]）诱导的变化。
根据 CRS 表型、表型和组织类型评估 ACE2 和 TMPRSS2 的表达。检查 ACE2/TMPRSS2 表达与鼻息肉（NP）中炎症介质之间的相关性。进行气液界面培养实验，以评估主要细胞因子或 poly（I:C）刺激对健康鼻黏膜、嗜酸性 NP（ENP）和非嗜酸性 NP（NENP）中初级上皮细胞 ACE2/TMPRSS2 表达的影响。
在原代鼻上皮细胞中，白细胞介素（IL）-13 降低 ACE2 的表达，但增加 TMPRSS2 的表达。无论 CRS 表型如何，嗜酸性 CRS 的 ACE2 表达均低于非嗜酸性 CRS。CRS 表型是 NP 中 ACE2/TMPRSS2 表达的独立相关因素。血清和组织嗜酸性粒细胞标志物水平与 ACE2 表达呈负相关，而 NP 组织中性粒细胞标志物水平与 ACE2 表达呈正相关。ENP 组织中 ACE2 的表达受到抑制；然而，poly（I:C）和 IL-13 的联合作用会诱导 ENP 中 ACE2/TMPRSS2 的上调。
ENP 组织中 ACE2 的表达低于 NENP；然而，病毒刺激会促进 ENP 中 ACE2/TMPRSS2 的上调。
