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Neutral sphingomyelinase-2, acid sphingomyelinase, and ceramide levels in COPD patients compared to controls

Authors Lea S, Metcalfe H, Plumb J, Beerli C, Poll C, Singh D, Abbott-Banner K

Received 2 September 2015

Accepted for publication 11 April 2016

Published 6 September 2016 Volume 2016:11(1) Pages 2139—2147

DOI https://doi.org/10.2147/COPD.S95578

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Professor Hsiao-Chi Chuang

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell


Simon R Lea,1,* Hannah J Metcalfe,1,* Jonathan Plumb,1 Christian Beerli,2 Chris Poll,3 Dave Singh,1 Katharine H Abbott-Banner3

1Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK; 2Novartis Pharma AG, Postfach, Basel, Switzerland; 3Respiratory Diseases, Novartis Institute for Biomedical Research, Horsham, West Sussex, UK

*These authors contributed equally to this work

Background: Increased pulmonary ceramide levels are suggested to play a causative role in lung diseases including COPD. Neutral sphingomyelinase-2 (nSMase-2) and acid SMase (aSMase), which hydrolyze sphingomyelin to produce ceramide, are activated by a range of cellular stresses, including inflammatory cytokines and pathogens, but notably cigarette smoke appears to only activate nSMase-2. Our primary objective was to investigate nSMase-2 and aSMase protein localization and quantification in lung tissue from nonsmokers (NS), smokers (S), and COPD patients. In addition, various ceramide species (C16, C18, and C20) were measured in alveolar macrophages from COPD patients versus controls.
Materials and methods: Patients undergoing surgical resection for suspected or confirmed lung cancer were recruited, and nSMase-2 and aSMase protein was investigated in different areas of lung tissue (small airways, alveolar walls, subepithelium, and alveolar macrophages) by immunohistochemistry. Ceramide species were measured in alveolar macrophages from COPD patients and controls by mass spectrometry.
Results: nSMase-2 and aSMase were detected in the majority of small airways. There was a significant increase in nSMase-2 immunoreactivity in alveolar macrophages from COPD patients (54%) compared with NS (31.7%) (P<0.05), and in aSMase immunoreactivity in COPD (68.2%) and S (69.5%) alveolar macrophages compared with NS (52.4%) (P<0.05). aSMase labeling was also increased in the subepithelium and alveolar walls of S compared with NS. Ceramide (C20) was significantly increased in alveolar macrophages from COPD patients compared with controls.
Conclusion: nSMase-2 and aSMase are both increased in COPD alveolar macrophages at the protein level; this may contribute toward the elevated ceramide (C20) detected in alveolar macrophages from COPD patients.

Keywords: sphingomyelinase, COPD, ceramide, cigarette smoke

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