| ApoE-deficient mice on cholate-containing high-fat diet reveal a pathology similar to lung sarcoidosis. | |
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MedLine Citation:
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PMID: 20093498 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sarcoidosis is a chronic disease of unknown etiology characterized by the formation of non-necrotizing epithelioid granulomas in various organs, especially in the lungs. The lack of an adequate animal model reflecting the pathogenesis of the human disease is one of the major impediments in studying sarcoidosis. In this report, we describe ApoE-/- mice on a cholate-containing high-fat diet that exhibit granulomatous lung inflammation similar to human sarcoidosis. Histological analysis revealed well-defined and non-necrotizing granulomas in about 40% of mice with the highest number of granulomas after 16 weeks on a cholate-containing high-fat diet. Granulomas contained CD4+ and CD8+ T cells, and the majority of the cells in granulomas showed immunoreactivity for the macrophage marker Mac-3. Cells with morphological features of epithelioid cells expressed angiotensin-converting enzyme, osteopontin, and cathepsin K, all characteristics of epithelioid and giant cells in granulomas of human sarcoidosis. Giant cells and nonspecific inclusions such as Schaumann's bodies and crystalline deposits were also detected in some lungs. Granulomatous inflammation resulted in progressive pulmonary fibrosis. Removal of cholate from the diet prevented the formation of lung granulomas. The observed similarities between the analyzed mouse lung granulomas and granulomas of human sarcoidosis, as well as the chronic disease character leading to fibrosis, suggest that this mouse model might be a useful tool to study sarcoidosis. |
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Authors:
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Andriy O Samokhin; Frank Bühling; Franz Theissig; Dieter Brömme |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-21 |
Journal Detail:
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Title: The American journal of pathology Volume: 176 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-10 Completed Date: 2010-06-07 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1148-56 Citation Subset: AIM; IM |
Affiliation:
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Department of Oral Science, Faculty of Dentistry, 2350 Health Sciences Mall, Life Sciences Institute, Room 4559, University of British Columbia, Vancouver V6T 1Z3, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Apolipoproteins E / deficiency*, metabolism Cathepsin K / metabolism Cholates / administration & dosage, pharmacology* Diet* Dietary Fats / administration & dosage, pharmacology* Female Granuloma / enzymology, pathology Humans Lung / enzymology, pathology Male Mice Mice, Inbred C57BL Middle Aged Pulmonary Fibrosis / complications, enzymology, pathology Sarcoidosis, Pulmonary / complications, enzymology, pathology* |
| Grant Support | |
ID/Acronym/Agency:
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MOP24447//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Cholates; 0/Dietary Fats; EC 3.4.22.38/Cathepsin K |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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