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

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Listed:
  • Ivan T. Lee

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Tsuguhisa Nakayama

    (Stanford University School of Medicine
    Jikei University School of Medicine)

  • Chien-Ting Wu

    (Stanford University School of Medicine)

  • Yury Goltsev

    (Stanford University School of Medicine)

  • Sizun Jiang

    (Stanford University School of Medicine)

  • Phillip A. Gall

    (Stanford University School of Medicine)

  • Chun-Kang Liao

    (National Taiwan University Hospital)

  • Liang-Chun Shih

    (China Medical University Hospital
    China Medical University
    China Medical University Hospital)

  • Christian M. Schürch

    (Stanford University School of Medicine)

  • David R. McIlwain

    (Stanford University School of Medicine)

  • Pauline Chu

    (Stanford University School of Medicine)

  • Nicole A. Borchard

    (Stanford University School of Medicine)

  • David Zarabanda

    (Stanford University School of Medicine)

  • Sachi S. Dholakia

    (Stanford University School of Medicine)

  • Angela Yang

    (Stanford University School of Medicine)

  • Dayoung Kim

    (Stanford University School of Medicine)

  • Han Chen

    (Stanford University School of Medicine)

  • Tomoharu Kanie

    (Stanford University School of Medicine)

  • Chia-Der Lin

    (China Medical University Hospital
    China Medical University
    China Medical University)

  • Ming-Hsui Tsai

    (China Medical University Hospital
    China Medical University
    China Medical University)

  • Katie M. Phillips

    (Stanford University School of Medicine)

  • Raymond Kim

    (Stanford University School of Medicine)

  • Jonathan B. Overdevest

    (Stanford University School of Medicine
    Columbia University School of Medicine)

  • Matthew A. Tyler

    (Stanford University School of Medicine
    University of Minnesota School of Medicine)

  • Carol H. Yan

    (Stanford University School of Medicine
    University of California San Diego School of Medicine)

  • Chih-Feng Lin

    (National Taiwan University Hospital)

  • Yi-Tsen Lin

    (National Taiwan University Hospital)

  • Da-Tian Bau

    (China Medical University
    China Medical University Hospital)

  • Gregory J. Tsay

    (China Medical University
    China Medical University Hospital)

  • Zara M. Patel

    (Stanford University School of Medicine)

  • Yung-An Tsou

    (China Medical University Hospital
    China Medical University)

  • Alexandar Tzankov

    (University Hospital Basel, University of Basel)

  • Matthias S. Matter

    (University Hospital Basel, University of Basel)

  • Chih-Jaan Tai

    (China Medical University Hospital
    China Medical University)

  • Te-Huei Yeh

    (National Taiwan University Hospital
    National Taiwan University)

  • Peter H. Hwang

    (Stanford University School of Medicine)

  • Garry P. Nolan

    (Stanford University School of Medicine)

  • Jayakar V. Nayak

    (Stanford University School of Medicine)

  • Peter K. Jackson

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

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.

Suggested Citation

  • Ivan T. Lee & Tsuguhisa Nakayama & Chien-Ting Wu & Yury Goltsev & Sizun Jiang & Phillip A. Gall & Chun-Kang Liao & Liang-Chun Shih & Christian M. Schürch & David R. McIlwain & Pauline Chu & Nicole A. , 2020. "ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19145-6
    DOI: 10.1038/s41467-020-19145-6
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    Cited by:

    1. Katharine K. Miller & Pei Wang & Nicolas Grillet, 2024. "SUB-immunogold-SEM reveals nanoscale distribution of submembranous epitopes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Andreia L. Pinto & Ranjit K. Rai & Jonathan C. Brown & Paul Griffin & James R. Edgar & Anand Shah & Aran Singanayagam & Claire Hogg & Wendy S. Barclay & Clare E. Futter & Thomas Burgoyne, 2022. "Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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