| Lung chitinolytic activity and chitotriosidase are elevated in chronic obstructive pulmonary disease and contribute to lung inflammation. | |
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MedLine Citation:
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PMID: 20042671 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and emphysematous alveolar destruction. In this study, we have investigated whether chitotriosidase (ChTRase) and acidic mammalian chitinase, two chitinases with chitinolytic activity, are selectively augmented in COPD and contribute to its pathogenesis. We found that smokers with COPD, but not asthmatics, had higher chitinolytic activity and increased levels of ChTRase in bronchoalveolar lavage, more ChTRase-positive cells in bronchial biopsies, and an elevated proportion of alveolar macrophages expressing ChTRase than smokers without COPD or never-smokers. ChTRase accounted for approximately 80% of bronchoalveolar lavage chitinolytic activity, while acidic mammalian chitinase was undetectable. Bronchoalveolar lavage chitinolytic activity and ChTRase were associated with airflow obstruction and emphysema and with the levels of interleukin (IL)-1beta, IL-8, tumor-necrosis factor (TNF)-alpha, and its type II soluble receptor. Tumor necrosis factor-alpha stimulated ChTRase release only from alveolar macrophages from smokers with COPD, and exposure of these cells to ChTRase promoted the release of IL-8, monocyte-chemoattractant protein-1, and metalloproteinase-9. Finally, ChTRase overexpression in the lung of normal mice promoted macrophage recruitment and the synthesis of the murine homologue of IL-8, keratinocyte-derived cytokine, and of monocyte-chemoattractant protein-1. We conclude that pulmonary ChTRase overexpression may represent a novel important mechanism involved in COPD onset and progression. |
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Authors:
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Séverine Létuvé; Alexander Kozhich; Alison Humbles; Yambasu Brewah; Marie-Christine Dombret; Martine Grandsaigne; Homa Adle; Roland Kolbeck; Michel Aubier; Anthony J Coyle; Marina Pretolani |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-30 |
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 Feb |
Date Detail:
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Created Date: 2010-01-26 Completed Date: 2010-03-16 Revised Date: 2011-07-22 |
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: 638-49 Citation Subset: AIM; IM |
Affiliation:
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Institut National de la Sante et de la RechercheMedicale (Inserm) U700, 75018 Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Asthma / metabolism, pathology Bronchoalveolar Lavage Fluid / chemistry Cells, Cultured Chitinase / metabolism*, physiology Cytokines / analysis, metabolism Female Hexosaminidases / metabolism*, physiology Humans Lung / enzymology*, metabolism, pathology Mice Mice, Inbred BALB C Pneumonia / etiology*, metabolism Pulmonary Disease, Chronic Obstructive / enzymology, immunology, metabolism*, pathology* Receptors, Cytokine / analysis, metabolism Smoking / metabolism Validation Studies as Topic |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Receptors, Cytokine; EC 3.2.1.-/Hexosaminidases; EC 3.2.1.-/chitotriosidase; EC 3.2.1.14/Chitinase |
| Comments/Corrections | |
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