Metcalfe, Hannah, Lea, Simon, Plumb, Jonathan, Beerli, Christian, Poll, Chris, Singh, Dave and Abbott-Banner, Katharine (2016) Neutral Sphingomyelinase-2, Acid Sphingomyelinase and Ceramide Levels in COPD patients compared to controls. International journal of chronic obstructive pulmonary disease, Volume (2016). pp. 2139-2147. ISSN 1178-2005

Abstract

Background: Increased pulmonary ceramide levels are suggested to play a causative role in lung diseases including chronic obstructive pulmonary disease (COPD). Neutral sphingomyelinase-2 (nSMase-2) and acid SMase (aSMase), which hydrolyse 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 localisation and quantification in lung tissue from non-smokers (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. 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 to NS (31.7%) (p<0.05), and in aSMase immunoreactivity in COPD (68.2%) and S (69.5%) alveolar macrophages compared to NS (52.4%) (p<0.05). aSMase labelling was also increased in the sub-epithelium and alveolar walls of S compared to NS. Ceramide (C20) was significantly increased in alveolar macrophages from COPD patients compared to controls. Conclusions: nSMase-2 and aSMase are both increased in COPD alveolar macrophages at the protein level; this may contribute towards the elevated ceramide (C20) detected in alveolar macrophages from COPD patients.

Item Type:	Article
Keywords:	sphingomyelinase, chronic obstructive pulmonary disease, ceramide, cigarette smoke
Date Deposited:	08 Sep 2016 00:45
Last Modified:	08 Sep 2016 00:45
URI:	https://oak.novartis.com/id/eprint/25893