PT  - JOURNAL ARTICLE
AU  - Rassin Lababidi
AU  - Jennifer Cane
AU  - Mona Bafadhel
TI  - Tight junction molecules are unresponsive in the epithelium of COPD patients during RV infection
AID  - 10.1183/13993003.congress-2021.PA3619
DP  - 2021 Sep 05
TA  - European Respiratory Journal
PG  - PA3619
VI  - 58
IP  - suppl 65
4099  - http://erj.ersjournals.com/content/58/suppl_65/PA3619.short
4100  - http://erj.ersjournals.com/content/58/suppl_65/PA3619.full
SO  - Eur Respir J2021 Sep 05; 58
AB  - 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.FootnotesCite 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).