Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid
(2021) In American Journal of Respiratory Cell and Molecular Biology 65(6). p.593-602- Abstract
Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and... (More)
Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.
(Less)
- author
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Respiratory Cell and Molecular Biology
- volume
- 65
- issue
- 6
- pages
- 593 - 602
- publisher
- American Thoracic Society
- external identifiers
-
- scopus:85120648416
- pmid:34192508
- ISSN
- 1535-4989
- DOI
- 10.1165/rcmb.2021-0064OC
- language
- English
- LU publication?
- yes
- id
- 6464449a-7040-41a6-aacc-111449142d71
- date added to LUP
- 2021-10-26 08:58:37
- date last changed
- 2024-03-23 12:15:19
@article{6464449a-7040-41a6-aacc-111449142d71, abstract = {{<p>Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.</p>}}, author = {{Padra, Médea and Benktander, John and Padra, János T and Andersson, Anders and Brundin, Bettina and Tengvall, Sara and Christenson, Karin and Qvarfordt, Ingemar and Gad, Robert and Paulsson, Magnus and Pournaras, Nikolaos and Lindén, Anders and Lindén, Sara K}}, issn = {{1535-4989}}, language = {{eng}}, number = {{6}}, pages = {{593--602}}, publisher = {{American Thoracic Society}}, series = {{American Journal of Respiratory Cell and Molecular Biology}}, title = {{Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid}}, url = {{http://dx.doi.org/10.1165/rcmb.2021-0064OC}}, doi = {{10.1165/rcmb.2021-0064OC}}, volume = {{65}}, year = {{2021}}, }