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Protein N-glycosylation in the bronchoalveolar space differs between never-smokers and long-term smokers with and without COPD

Venkatakrishnan, Vignesh ; Thomsson, Kristina A ; Padra, Médea LU orcid ; Andersson, Anders ; Brundin, Bettina ; Christenson, Karin ; Bylund, Johan ; Karlsson, Niclas G ; Lindén, Anders and Lindén, Sara K (2023) In Glycobiology 33(12). p.1128-1138
Abstract

Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n = 5) and long-term... (More)

Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n = 5) and long-term smokers (LTS) with (LTS+, n = 4) and without COPD (LTS-, n = 8). Using mass spectrometry, we identified 57 highly confident N-glycan structures whereof 38 oligomannose, complex, and paucimannose type glycans were common to BAL samples from HNS, LTS- and LTS+ groups. Hybrid type N-glycans were identified only in the LTS+ group. Qualitatively and quantitatively, HNS had lower inter-individual variation between samples compared to LTS- or LTS+. Cluster analysis of BAL N-glycosylation distinguished LTS from HNS. Correlation analysis with clinical parameters revealed that complex N-glycans were associated with health and absence of smoking whereas oligomannose N-glycans were associated with smoking and disease. The N-glycan profile from monocyte-derived macrophages differed from the BAL N-glycan profiles. In conclusion, long-term smokers display substantial alterations of N-glycosylation in the bronchoalveolar space, and the hybrid N-glycans identified only in long-term smokers with COPD deserve to be further studied as potential biomarkers.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Humans, Smokers, Glycosylation, Pulmonary Disease, Chronic Obstructive/metabolism, Smoking, Biomarkers/metabolism, Polysaccharides, Bronchoalveolar Lavage Fluid/chemistry
in
Glycobiology
volume
33
issue
12
pages
1128 - 1138
publisher
Oxford University Press
external identifiers
  • pmid:37656214
  • scopus:85185768954
ISSN
1460-2423
DOI
10.1093/glycob/cwad071
language
English
LU publication?
no
additional info
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
id
53ebc2ce-c237-4525-b42d-9cfa9ff42d91
date added to LUP
2026-09-02 12:17:34
date last changed
2026-09-04 03:32:27
@article{53ebc2ce-c237-4525-b42d-9cfa9ff42d91,
  abstract     = {{<p>Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n = 5) and long-term smokers (LTS) with (LTS+, n = 4) and without COPD (LTS-, n = 8). Using mass spectrometry, we identified 57 highly confident N-glycan structures whereof 38 oligomannose, complex, and paucimannose type glycans were common to BAL samples from HNS, LTS- and LTS+ groups. Hybrid type N-glycans were identified only in the LTS+ group. Qualitatively and quantitatively, HNS had lower inter-individual variation between samples compared to LTS- or LTS+. Cluster analysis of BAL N-glycosylation distinguished LTS from HNS. Correlation analysis with clinical parameters revealed that complex N-glycans were associated with health and absence of smoking whereas oligomannose N-glycans were associated with smoking and disease. The N-glycan profile from monocyte-derived macrophages differed from the BAL N-glycan profiles. In conclusion, long-term smokers display substantial alterations of N-glycosylation in the bronchoalveolar space, and the hybrid N-glycans identified only in long-term smokers with COPD deserve to be further studied as potential biomarkers.</p>}},
  author       = {{Venkatakrishnan, Vignesh and Thomsson, Kristina A and Padra, Médea and Andersson, Anders and Brundin, Bettina and Christenson, Karin and Bylund, Johan and Karlsson, Niclas G and Lindén, Anders and Lindén, Sara K}},
  issn         = {{1460-2423}},
  keywords     = {{Humans; Smokers; Glycosylation; Pulmonary Disease, Chronic Obstructive/metabolism; Smoking; Biomarkers/metabolism; Polysaccharides; Bronchoalveolar Lavage Fluid/chemistry}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  pages        = {{1128--1138}},
  publisher    = {{Oxford University Press}},
  series       = {{Glycobiology}},
  title        = {{Protein N-glycosylation in the bronchoalveolar space differs between never-smokers and long-term smokers with and without COPD}},
  url          = {{http://dx.doi.org/10.1093/glycob/cwad071}},
  doi          = {{10.1093/glycob/cwad071}},
  volume       = {{33}},
  year         = {{2023}},
}