Expression of SARS-CoV-2 Entry Factors in Human Alveolar Type II Cells in Aging and Emphysema.

Chih-Ru Lin,Beata Kosmider,Nathaniel Marchetti,Hannah Simborio,Gerard J Criner,Sudhir Bolla,Karim Bahmed,Hassan Hayek

doi:10.3390/biomedicines9070779

Abstract

Alveolar type II (ATII) cells proliferate and restore the injured epithelium. It has been described that SARS-CoV-2 infection causes diffuse alveolar damage in the lungs. However, host factors facilitating virus infection in ATII cells are not well known. We determined the SARS-CoV-2-related genes and protein expression using RT-PCR and Western blotting, respectively, in ATII cells isolated from young and elderly non-smokers, smokers, and ex-smokers. Cells were also obtained from lung transplants of emphysema patients. ACE2 has been identified as the receptor for SARS-CoV-2, and we found significantly increased levels in young and elderly smokers and emphysema patients. The viral entry depends on TMPRSS2 protease activity, and a higher expression was detected in elderly smokers and ex-smokers and emphysema patients. Both ACE2 and TMPRSS2 mRNA levels were higher in this disease in comparison with non-smokers. CD209L serves as a receptor for SARS-CoV-2, and we found increased levels in ATII cells obtained from smokers and in emphysema patients. Also, our data suggest CD209L regulation by miR142. Endoplasmic reticulum stress was detected in ATII cells in this disease. Our results suggest that upregulation of SARS-CoV-2 entry factors in ATII cells in aging, smokers, and emphysema patients may facilitate infection.

Highlights

Published: 6 July 2021The alveolar epithelium is the barrier between inhaled air and the underlying tissue and is composed of alveolar type II (ATII) and alveolar type I cells [1]
We analyzed the expression of genes and proteins related to SARS-CoV-2 entry using Alveolar type II (ATII) cells obtained from young and elderly non-smokers and smokers and emphysema patients to improve our knowledge
We found increased ACE2 protein and gene expression in ATII cells isolated from emphysema patients compared to nonsmokers

Summary

Introduction

The alveolar epithelium is the barrier between inhaled air and the underlying tissue and is composed of alveolar type II (ATII) and alveolar type I cells [1]. ATII cells have a stem cell potential, as they proliferate and repair the epithelium after damage. Re-epithelialization is orchestrated principally by ATII cells, and this indicates their critical role in lung function. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the COVID-19 outbreak leading to acute respiratory distress syndrome [2]. Pathological examination of the biopsy samples obtained from deceased COVID-19 patients revealed diffuse alveolar damage in the lungs [3]. The mechanism is not well understood, and there is a gap in our knowledge of host factors, cell-cell interactions, and proteases that play a significant role in SARS-CoV-2 infection.

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Conclusion