| Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease. | |
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MedLine Citation:
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PMID: 20395562 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Malcolm Brodlie; Michael C McKean; Gail E Johnson; Joe Gray; Andrew J Fisher; Paul A Corris; James L Lordan; Christopher Ward |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-15 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 182 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-09-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 369-75 Citation Subset: AIM; IM |
Affiliation:
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Sir William Leech Centre For Lung Research, Freeman Hospital, Newcastle upon Tyne, UK. m.j.brodlie@ncl.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Ceramides / metabolism* Chromatography, High Pressure Liquid Cystic Fibrosis / metabolism*, pathology Humans Hypertension, Pulmonary / metabolism, pathology Immunohistochemistry Leukocyte Elastase / metabolism Lung / metabolism, microbiology Mass Spectrometry Middle Aged Peroxidase / metabolism Pseudomonas aeruginosa Pulmonary Emphysema / metabolism, pathology Respiratory Mucosa / metabolism* Severity of Illness Index |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Ceramides; EC 1.11.1.7/Peroxidase; EC 3.4.21.37/Leukocyte Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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