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Lookup NU author(s): Dr Malcolm Brodlie, Dr Michael McKean, Dr Joseph Gray, Professor Andrew FisherORCiD, Dr James Lordan, Professor Christopher WardORCiD
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Rationale: Ceramide accumulates in the airway epithelium of mice deficient in cystic fibrosis transmembrane conductance regulator, resulting in susceptibility to Pseudomonas aeruginosa infection and inflammation.Objectives: To investigate quantitatively ceramide levels in the lower airway of people with cystic fibrosis compared with pulmonary hypertension, emphysema, and lung donors.Methods: Immunohistochemistry was performed on the lower airway epithelium of explanted lungs (eight cystic fibrosis, emphysema, and pulmonary hypertension, respectively) and eight donor lungs using ceramide, neutrophil elastase, and myeloperoxidase antibodies. High-performance liquid chromatography–mass spectrometry was performed on tissue from five lungs with cystic fibrosis and five with pulmonary hypertension.Measurements and Main Results: Staining for ceramide was significantly increased in the lower airway epithelium of people with cystic fibrosis (median, 14.11%) compared with pulmonary hypertension (3.03%; P = 0.0009); unused lung donors (3.44%; P = 0.0009); and emphysema (5.06%; P = 0.01). Ceramide staining was increased in emphysematous lungs compared with pulmonary hypertension (P = 0.0135) and unused donors (P = 0.0009). The number of neutrophil elastase– and myeloperoxidase-positive cells in the airway was positively correlated with the percentage of epithelium staining for ceramide (P = 0.001). Ceramide staining was significantly increased in lungs colonized with Pseudomonas aeruginosa (10.1%) compared with those not colonized (3.14%; P = 0.0106). Significantly raised levels of ceramides C16:0, C18:0, and C20:0 were detected by mass spectrometry in lungs with cystic fibrosis compared with pulmonary hypertension. Differences in C22:0 were not significant.Conclusions: Immunoreactive ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis. Detected by mass-spectrometry ceramide species C16:0, C18:0, and C20:0 but not C22:0 are increased.
Author(s): Brodlie M, McKean MC, Johnson GE, Gray J, Fisher AJ, Corris PA, Lordan JL, Ward C
Publication type: Article
Publication status: Published
Journal: American Journal of Respiratory and Critical Care Medicine
Year: 2010
Volume: 182
Issue: 3
Pages: 369-375
Print publication date: 15/04/2010
ISSN (print): 1073-449X
ISSN (electronic): 1535-4970
Publisher: American Thoracic Society
URL: http://dx.doi.org/10.1164/rccm.200905-0799OC
DOI: 10.1164/rccm.200905-0799OC
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