Mucin Binding to Moraxella catarrhalis during Airway Inflammation Is Dependent on Sialic Acid

• Published in: American journal of respiratory cell and molecular biology Vol. 65; no. 6; pp. 593 - 602
• Main Authors: Padra, Médea, Benktander, John, Padra, János T., Andersson, Anders, Brundin, Bettina, Tengvall, Sara, Christenson, Karin, Qvarfordt, Ingemar, Gad, Robert, Paulsson, Magnus, Pournaras, Nikolaos, Lindén, Anders, Lindén, Sara K.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.12.2021
• Subjects: Airway management; Basic Medicine; C-reactive protein; Chronic obstructive pulmonary disease; Clinical Medicine; COPD; Cytokines; Glycosylation; host–pathogen interaction; Humans; Immunologi inom det medicinska området; Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi); Immunology in the Medical Area; Immunology in the Medical Area (including Cell and Immunotherapy); Inflammation; Klinisk medicin; Lactose; Lung - metabolism; Lung - microbiology; Lung diseases; Lungmedicin och allergi; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the Medical Area; Mikrobiologi inom det medicinska området; Moraxella catarrhalis; Moraxella catarrhalis - metabolism; Mucin; Mucin-5B - metabolism; Mucus; N-Acetylneuraminic acid; Obstructive lung disease; Pathogens; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - microbiology; Respiratory function; Respiratory Medicine and Allergy; Respiratory Mucosa - metabolism; Respiratory Mucosa - microbiology; Respiratory tract; Respiratory tract diseases; sialic acid; Sialic Acids - metabolism; Moraxella catarrhalis; sialic acid; mucin; host–pathogen interaction; COPD
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2021-0064OC

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 (  = 4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was -acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and -acetyl-hexoseamine among never-smokers. bound to MUC5 mucins from smokers with and without COPD. binding correlated with inflammatory parameters and Neu5Ac content. binding was abolished by enzymatic removal of Neu5Ac. Furthermore, bound to α2,6 sialyl-lactose, suggesting that α2,6 sialic acid contributes to binding to mucins. Furthermore, we detected more binding to mucins from patients with pneumonia than to those from control subjects (  = 8-13), and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation-induced Neu5Ac in the adhesion of to airway mucins. The inflammation-induced ability of MUC5 mucins to bind 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 patients with COPD.