Studies of chronic obstructive pulmonary disease (COPD) using animal models and patient plasma indicate dysregulation of sphingolipid metabolism, but data in COPD lungs are sparse. Mass spectrometric and immunostaining measurements of lungs from 69 COPD, 16 smokers without COPD and 13 subjects with interstitial lung disease identified decoupling of lung ceramide and sphingosine-1 phosphate (S1P) levels and decreased sphingosine kinase-1 (SphK1) activity in COPD. The correlation of ceramide abundance in distal COPD lungs with apoptosis and the inverse correlation between SphK1 activity and presence of emphysema suggest that disruption of ceramide-to-S1P metabolism is an important determinant of emphysema phenotype in COPD.
- COPD pathology
- tobacco and the lung
- interstitial fibrosis
- COPD exacerbations mechanisms
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Contributors EVB designed and performed experiments and analysed and interpreted data. KAS analysed data and participated in manuscript writing. KSS coordinated experiments and participated in manuscript writing. IB performed data analyses. AM performed statistical analyses. IP designed and coordinated experiments, performed data analysis and interpretation and wrote the manuscript.
Funding The research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers RO3HL095440 (EVB and IP) and RO1HL077328 (IP).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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