| Affiliation: | 1. Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada;2. Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada;3. Department of Cardiovascular & Respiratory Sciences, University of Calgary, Calgary, Alberta, Canada;4. Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada;5. Pediatric Cystic Fibrosis Clinic, Alberta Children''s Hospital, Calgary, Alberta, Canada;6. Department of Surgery, Alberta Children''s Hospital, Calgary, Alberta, Canada;7. SolAeroMed Inc., Calgary, Alberta, Canada |
| Abstract: | BackgroundAirway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation.MethodsSurfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD).ResultsCF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products.ConclusionWe confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF. |
