Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146192-e0146192
• Main Authors: Gela, Anele, Bhongir, Ravi K V, Mori, Michiko, Keenan, Paul, Mörgelin, Matthias, Erjefält, Jonas S, Herwald, Heiko, Egesten, Arne, Kasetty, Gopinath
• Format: Article
• Language: English
• Subjects: Antibacterial activity; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Bacterial Infections - complications; Bacterial Infections - metabolism; beta-Defensins - metabolism; Binding; Biocompatibility; Biomedical materials; Care and treatment; Chemokines; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Clinical Medicine; Complications and side effects; Cystic fibrosis; Cytokines; Cytokines - metabolism; Elastase; Glycoproteins; Growth factors; Haemophilus influenzae; Health aspects; Health risks; Humans; Immunoglobulins; Infections; Infectious diseases; Inflammation; Klinisk medicin; Lactoferrin; Lactoferrin - metabolism; Leukocytes; Lung - metabolism; Lung diseases; Lungmedicin och allergi; Lysozyme; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Midkine; Molecular biology; Neutrophils; Obstructive lung disease; Osteopontin; Osteopontin - metabolism; Peptidase; Protein Binding; Proteins; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - microbiology; R&D; Research & development; Respiratory Medicine and Allergy; Respiratory tract; Respiratory tract diseases; Respiratory Tract Infections - complications; Respiratory Tract Infections - metabolism; Respiratory Tract Infections - microbiology; Risk factors; Secretory Leukocyte Peptidase Inhibitor - metabolism; Shielding; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - isolation & purification; Thymic stromal lymphopoietin; Thymus; Treatment Failure; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146192

Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN), a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI), midkine, human beta defensin-3 (hBD-3), and thymic stromal lymphopoietin (TSLP) but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD.