Lasantha Gunasekara1, Mustafa Al-Saiedy2, Francis Green3, Ryan Pratt1, Candice Bjornson4, Ailian Yang5, W Michael Schoel6, Ian Mitchell4, Mary Brindle7, Mark Montgomery4, Elizabeth Keys8, John Dennis9, Grishma Shrestha8, Matthias Amrein10. 1. Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada. 2. Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada; Department of Cardiovascular & Respiratory Sciences, University of Calgary, Calgary, Alberta, Canada. 3. Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada; Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: fgreen@ucalgary.ca. 4. Pediatric Cystic Fibrosis Clinic, Alberta Children's Hospital, Calgary, Alberta, Canada. 5. Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada. 6. Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada. 7. Department of Surgery, Alberta Children's Hospital, Calgary, Alberta, Canada. 8. Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada. 9. SolAeroMed Inc., Calgary, Alberta, Canada. 10. Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada. Electronic address: mamrein@ucalgary.ca.
Abstract
BACKGROUND: Airway 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. METHODS: Surfactant 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). RESULTS: CF 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. CONCLUSION: We 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.
BACKGROUND: Airway 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. METHODS: Surfactant 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). RESULTS:CF 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. CONCLUSION: We confirm that CFpatients 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.
Authors: Mustafa Al-Saiedy; Lasantha Gunasekara; Francis Green; Ryan Pratt; Andrea Chiu; Ailian Yang; John Dennis; Cora Pieron; Candice Bjornson; Brent Winston; Matthias Amrein Journal: Mil Med Date: 2018-03-01 Impact factor: 1.437
Authors: Christina W Agudelo; Britta K Kumley; Estela Area-Gomez; Yimeng Xu; Abdoulaye J Dabo; Patrick Geraghty; Michael Campos; Robert Foronjy; Itsaso Garcia-Arcos Journal: PLoS One Date: 2020-02-06 Impact factor: 3.240
Authors: Manuel Torres; Catalina Ana Rosselló; Paula Fernández-García; Victoria Lladó; Or Kakhlon; Pablo Vicente Escribá Journal: Int J Mol Sci Date: 2020-03-27 Impact factor: 5.923