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

Autor: Jonathan Plumb, Dave Singh, Hannah J. Metcalfe, Christian Beerli, Simon Lea, Chris Poll, Katharine Abbott-Banner
Rok vydání: 2016
Předmět:
Zdroj: Lea, S, Metcalfe, H J, Plumb, J, Beerli, C, Poll, C, Singh, D & Abbott-Banner, K H 2016, ' Neutral sphingomyelinase-2, acid sphingomyelinase, and ceramide levels in COPD patients compared to controls ', International journal of chronic obstructive pulmonary disease, vol. 11, no. 1, pp. 2139-2147 . https://doi.org/10.2147/COPD.S95578
International Journal of Chronic Obstructive Pulmonary Disease
ISSN: 1178-2005
DOI: 10.2147/copd.s95578
Popis: 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
Databáze: OpenAIRE