Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid

Padra, Médea ; Benktander, John ; Padra, János T ; Andersson, Anders LU ; Brundin, Bettina ; Tengvall, Sara ; Christenson, Karin ; Qvarfordt, Ingemar ; Gad, Robert LU and Paulsson, Magnus LU orcid , et al. (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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
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}},
}