ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.

Autor: Lee IT; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA., Nakayama T; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan., Wu CT; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA., Goltsev Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Jiang S; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Gall PA; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Liao CK; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan., Shih LC; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.; Terry Fox Cancer Research Laboratory, Translational Medicine Center, China Medical University Hospital, Taichung, Taiwan., Schürch CM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., McIlwain DR; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Chu P; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Borchard NA; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Zarabanda D; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Dholakia SS; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Yang A; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Kim D; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Chen H; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Kanie T; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA., Lin CD; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.; School of Medicine, China Medical University, Taichung, Taiwan., Tsai MH; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.; School of Medicine, China Medical University, Taichung, Taiwan., Phillips KM; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Kim R; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Overdevest JB; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Otolaryngology-Head and Neck Surgery, Columbia University School of Medicine, New York City, NY, USA., Tyler MA; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Otolaryngology-Head and Neck Surgery, University of Minnesota School of Medicine, Minneapolis, MN, USA., Yan CH; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego School of Medicine, San Diego, CA, USA., Lin CF; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan., Lin YT; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan., Bau DT; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.; Terry Fox Cancer Research Laboratory, Translational Medicine Center, China Medical University Hospital, Taichung, Taiwan., Tsay GJ; School of Medicine, China Medical University, Taichung, Taiwan.; Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan., Patel ZM; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Tsou YA; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.; School of Medicine, China Medical University, Taichung, Taiwan., Tzankov A; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland., Matter MS; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland., Tai CJ; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.; School of Medicine, China Medical University, Taichung, Taiwan., Yeh TH; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.; Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan., Hwang PH; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Nolan GP; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA. gnolan@stanford.edu., Nayak JV; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA., Jackson PK; Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Oct 28; Vol. 11 (1), pp. 5453. Date of Electronic Publication: 2020 Oct 28.
DOI: 10.1038/s41467-020-19145-6
Abstrakt: The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.
Databáze: MEDLINE