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 mucin 5AC (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 viral 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 RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.
Aran Singanayagam, Joseph Footitt, Matthias Marczynski, Giorgia Radicioni, Michael T. Cross, Lydia J. Finney, Maria-Belen Trujillo-Torralbo, Maria Calderazzo, Jie Zhu, Julia Aniscenko, Thomas B. Clarke, Philip L. Molyneaux, Nathan W. Bartlett, Miriam F. Moffatt, William O. Cookson, Jadwiga Wedzicha, Christopher M. Evans, Richard C. Boucher, Mehmet Kesimer, Oliver Lieleg, Patrick Mallia, Sebastian L. Johnston
Usage data is cumulative from May 2023 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,628 | 555 |
1,180 | 171 | |
Figure | 359 | 5 |
Table | 91 | 0 |
Supplemental data | 60 | 6 |
Citation downloads | 41 | 0 |
Totals | 3,359 | 737 |
Total Views | 4,096 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.