Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice.
Am J Respir Crit Care Med
; 177(7): 730-42, 2008 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-18079494
ABSTRACT
RATIONALE Chronic obstructive pulmonary disease is a leading cause of death worldwide, but its pathogenesis is not well understood. Previous studies have shown that airway surface dehydration in beta-epithelial Na(+) channel (betaENaC)-overexpressing mice caused a chronic lung disease with high neonatal pulmonary mortality and chronic bronchitis in adult survivors. OBJECTIVES:
The aim of this study was to identify the initiating lesions and investigate the natural progression of lung disease caused by airway surface dehydration.METHODS:
Lung morphology, gene expression, bronchoalveolar lavage, and lung mechanics were studied at different ages in betaENaC-overexpressing mice. MEASUREMENTS AND MAINRESULTS:
Mucus obstruction in betaENaC-overexpressing mice originated in the trachea in the first days of life and was associated with hypoxia, airway epithelial necrosis, and death. In surviving betaENaC-overexpressing mice, mucus obstruction extended into the lungs and was accompanied by goblet cell metaplasia, increased mucin expression, and airway inflammation with transient perinatal increases in tumor necrosis factor-alpha and macrophages, IL-13 and eosinophils, and persistent increases in keratinocyte-derived cytokine (KC), neutrophils, and chitinases in the lung. betaENaC-overexpressing mice also developed emphysema with increased lung volumes, distal airspace enlargement, and increased lung compliance.CONCLUSIONS:
Our studies demonstrate that airway surface dehydration is sufficient to initiate persistent neutrophilic airway inflammation with chronic airways mucus obstruction and to cause transient eosinophilic airway inflammation and emphysema. These results suggest that deficient airway surface hydration may play a critical role in the pathogenesis of chronic obstructive pulmonary diseases of different etiologies and serve as a target for novel therapies.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Mucosa Respiratória
/
Doença Pulmonar Obstrutiva Crônica
/
Canais Epiteliais de Sódio
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Alemanha