The Relationship of Chronic Mucin Secretion to Airway Disease in Normal and CFTR-Deficient Mice
| Autor: | Beverly H. Koller, William K. Funkhouser, Elizabeth M. Hicks, Dana C. Backlund, Victoria L. Cressman |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Pulmonary and Respiratory Medicine
Ovalbumin Respiratory Tract Diseases Clinical Biochemistry Cystic Fibrosis Transmembrane Conductance Regulator Gene Expression Biology medicine.disease_cause Cystic fibrosis Microbiology Mice Respiratory Hypersensitivity medicine Animals Pseudomonas Infections Secretion RNA Messenger Molecular Biology Mice Inbred BALB C Hyperplasia Reverse Transcriptase Polymerase Chain Reaction Pseudomonas aeruginosa Respiratory disease Mucins Cell Biology Staphylococcal Infections respiratory system medicine.disease Mucus Pathophysiology Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Mice Inbred C57BL Mice Inbred DBA Immunology biology.protein Goblet Cells Airway |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 19:853-866 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.19.6.3194 |
| Popis: | In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus. The mechanism underlying the pathophysiology of the disease in humans has not been established. However, it has been suggested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth. If this hypothesis is correct, it could explain the absence of respiratory disease in CFTR-deficient mice, since mice have only a single submucosal gland and display few goblet cells in their lower airways, even when exposed to bacteria. To test this hypothesis further, we induced allergic airway disease in CFTR-deficient mice. We found that induction of allergic airway disease in mice, unlike bacterial infection, results in an inflammatory response characterized by goblet cell hyperplasia, increased mucin gene expression, and increased production of mucus. However, we also found that disease progression and resolution is identical in Cftr-/- mice and control animals. Furthermore, we show that the presence of mucus in the Cftr-/- airway does not lead to chronic airway disease, even upon direct inoculation with S. aureus and P. aeruginosa. Therefore, factors in addition to the absence of high levels of mucus secretion protect the mouse from the airway disease seen in human CF patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|