High Levels of Protein in COPD Patients’ Airways Can Increase Risk of Infection
Researchers discovered that patients with chronic obstructive pulmonary disease (COPD) show increased levels of a protein that inhibits the immune system response against several pathogens, thereby increasing their vulnerability to infections. The study, “Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics,” was published in the open access journal PLOS One.
COPD is a type of obstructive lung disease characterized by persistent inflammation, which causes narrowing of the airways. As a consequence of this narrowing, COPD carriers experience a chronically poor airflow, characterized by symptoms such as shortness of breath, cough, and sputum production. COPD exacerbation periods (a flare-up or episode when the breathing gets worse than usual) are often caused by bacterial infections, with most common agents being Pseudomonas aeruginosa, non-typeable Haemophilus influenza, Streptococcus pneumoniae, and Branhamella catarrhalis.
Increasingly recognized is the risk among COPD carriers to suffer from invasive pneumococcal disease (IPD). The mechanisms underlying this increased risk remain poorly understood, but include a defective mucus clearance and structural remodeling of the airways.
Antimicrobial proteins (AMPs) play key roles in airway innate immunity, and different AMPs are expressed, among other cells, by airway epithelial cells. Examples of AMPs are lysozyme, lactoferrin, secretory leukocyte peptidase inhibitor (SLPI), midkine, defensins, thymic stromal lymphopietin (TSLP) and the cathelicidin-derived peptide LL-37.
The research team investigated the role of osteopontin, a glycoprotein highly upregulated in the airways of COPD patients. The levels of osteopontin increase increase with the severity of the disease. They found that osteopontin co-localizes with several AMPs in airways. In lab studies, researchers observed that osteopontin bound to lactoferrin, SLPI, midkine, human beta defensin-3 (hBD-3), and TSLP, but did not bind (or very little, anyway) to lysozyme and LL-37.
When osteopontin bound to antimicrobial proteins, it reduced its antibacterial activity against two key airway pathogens, Streptococcus pneumoniae and Pseudomonas aeruginosa. In fact, osteopontin reduced lysozyme-induced killing of Streptococcus pneumoniae.
The findings suggest that an increased level of osteopontin in COPD patients impairs the host defense by decreasing the bacterial activity of several antimicrobial proteins, ultimately leading to an increased risk among COPD patients of infections from airway bacteria.