Chronic Pseudomonas aeruginosa infection-induced chronic bronchitis and emphysematous changes in CCSP-deficient mice

Abstract

The club cell secretory protein (CCSP) is a regulator of lung inflammation following acute respiratory infection or lung injury. Recently, the relationship between CCSP and COPD has been reported. Since COPD results from an abnormal inflammatory response, we hypothesized that CCSP could have a protective role against chronic inflammation-induced lung damage. To address this issue, the pathophysiology of chronic lung inflammation induced by Pseudomonas aeruginosa in CCSP-deficient mice was determined. A tube of 5 mm in length was soaked in a fluid containing P. aeruginosa (PAO01 strain) for 1 week and inserted into the trachea of CCSP-deficient mice. One week later, P. aeruginosa was administered into the trachea. Five weeks after insertion of tube, the mice were sacrificed. Bronchoalveolar lavage fluids were collected to determine the bacterial growth, and the lung histology and physiology were also examined. P. aeruginosa was continuously detected in bronchoalveolar lavage fluids during the study. Neutrophils were increased in the bronchoalveolar lavage fluids from the CCSP-deficient mice in comparison to wild-type mice. A histological study demonstrated chronic inflammation around bronchus, serious bronchial stenosis, and alveolar enlargement in the CCSP-deficient mice. The lung physiology study demonstrated an increase in the lung compliance of the CCSP-deficient mice. Chronic P. aeruginosa inflammation resulted in chronic bronchitis and emphysematous changes in the CCSP-deficient mice. CCSP could play an important role in protecting the host from the chronic inflammation-induced lung damage.

Keywords:

• chronic bronchitis
• animal models
• emphysema
• inflammation

Acknowledgments

The authors appreciate the assistance of Dr Brian Quinn with language editing. The study was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (No 14570553 [to MF]), and funding from Astra-Zeneca Research Fellow 2003 (to MF). An abstract of part of the study has been presented in an international conference: Matsumoto T, Fujita M, Hirano R, Tashiro N, Asai Y, Fukuyama S, Morimoto Y, Nakanishi Y, Watanabe K. Chronic Infection of Pseudomonas aeruginosa induced COPD like changes in CCSP-deficient mice. Abstract no A2697. ATS, May 16–21, 2014, San Diego, CA, USA.

Author contributions

All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.