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Tight junction molecules are unresponsive in the epithelium of COPD patients during RV infection

Rassin Lababidi, Jennifer Cane, Mona Bafadhel
European Respiratory Journal 2021 58: PA3619; DOI: 10.1183/13993003.congress-2021.PA3619
Rassin Lababidi
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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  • For correspondence: rassin.lababidi@seh.ox.ac.uk
Jennifer Cane
2NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
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Mona Bafadhel
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Abstract

Introduction: The lung epithelium is a protective barrier against pathogens. Rhinovirus (RV) infections are linked to COPD exacerbations. Epithelial barrier function during viral infection is not well understood in COPD.

Objectives: We sought to examine changes in tight junctions (TJ) in the bronchial epithelium in COPD patients compared to smokers and healthy controls, and changes in barrier integrity upon RV infection.

Methods: Human Bronchial Epithelial Cells (HBECs) in submerged cultured grown to 90% confluence from COPD patients (n=5), smokers (n=2), and healthy (n=3) controls were stimulated with RV16 at 0.1 MOI for 24 hours. We measured mean fluorescence intensity (MFI) of TJ molecules CLDN-3, CLDN-4, and JAM-A from confocal microscopy images.

Results: COPD (Medians: 4747, 8115, 2516) (p=0.0002, p=0.0007, p=0.021) and smoker (Medians: 4861, 4310, 3747) (p=0.018, p=0.0253, p<0.0001) HBECs at basal conditions had significantly more TJ molecules compared to healthy controls (Medians: 2553, 2522, 1905). CLDN-3, CLDN-4, and JAM-A significantly increased in response to RV16 infection in healthy HBECs (Medians: 4714, 4925, 2720) (p=0.0355, p=0.0094, p=0.0095) while COPD HBECs were unresponsive except for CLDN-3 (Median: 6435, p=0.0478). HBECs from smokers had significantly decreased CLDN-3 and JAM-A in response to RV16 (Median: 3466 and 2046) (p=0.0041, p=0.0021) infection while CLDN-4 was unchanged.

Conclusions: TJs from smokers and COPD patients are largely unresponsive to RV infection compared to healthy HBECs but are expressed at significantly higher levels at basal conditions. These data indicate that the epithelium is dysregulated in smokers and COPD.

  • COPD
  • Viruses
  • Epithelial cell

Footnotes

Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3619.

This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2021
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Tight junction molecules are unresponsive in the epithelium of COPD patients during RV infection
Rassin Lababidi, Jennifer Cane, Mona Bafadhel
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3619; DOI: 10.1183/13993003.congress-2021.PA3619

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Tight junction molecules are unresponsive in the epithelium of COPD patients during RV infection
Rassin Lababidi, Jennifer Cane, Mona Bafadhel
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3619; DOI: 10.1183/13993003.congress-2021.PA3619
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