Imperial College London
Portrait Picture

DrThomasClarke

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 2074thomas.clarke

 
 
//

Location

 

5.40DFlowers buildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Singanayagam:2022:10.1172/JCI120901,
author = {Singanayagam, A and Footitt, J and Marczynski, M and Radicioni, G and Cross, MT and Finney, LJ and Trujillo-Torralbo, M-B and Calderazzo, MA and Zhu, J and Aniscenko, J and Clarke, TB and Molyneaux, PL and Bartlett, NW and Moffatt, MF and Cookson, WO and Wedzicha, JA and Evans, CM and Boucher, RC and Kesimer, M and Lieleg, O and Mallia, P and Johnston, SL},
doi = {10.1172/JCI120901},
journal = {Journal of Clinical Investigation},
pages = {1--16},
title = {Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.},
url = {http://dx.doi.org/10.1172/JCI120901},
volume = {132},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway MUC5AC and MUC5B concentrations during spontaneous and experimentally-induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with virus load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation as Muc5ac-deficient (Muc5ac-/-) mice had attenuated rhinovirus (RV)-induced airway inflammation and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of rhinovirus-induced inflammation in mice. Therapeutic suppression of mucin production using an epidermal growth factor receptor (EGFR) antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identifies a pro-inflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.
AU  - Singanayagam,A
AU  - Footitt,J
AU  - Marczynski,M
AU  - Radicioni,G
AU  - Cross,MT
AU  - Finney,LJ
AU  - Trujillo-Torralbo,M-B
AU  - Calderazzo,MA
AU  - Zhu,J
AU  - Aniscenko,J
AU  - Clarke,TB
AU  - Molyneaux,PL
AU  - Bartlett,NW
AU  - Moffatt,MF
AU  - Cookson,WO
AU  - Wedzicha,JA
AU  - Evans,CM
AU  - Boucher,RC
AU  - Kesimer,M
AU  - Lieleg,O
AU  - Mallia,P
AU  - Johnston,SL
DO  - 10.1172/JCI120901
EP  - 16
PY  - 2022///
SN  - 0021-9738
SP  - 1
TI  - Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI120901
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35239513
UR  - https://www.jci.org/articles/view/120901
UR  - http://hdl.handle.net/10044/1/95485
VL  - 132
ER  -
Download