Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice

Respiratory Research

Uma S Sajjan³  James M Beck²  Peter Mancuso¹  Brenton Kinker³  Adam T Comstock³  Shyamala Ganesan³ 

[1] School of Public Health, University of Michigan, Ann Arbor, MI, USA;Veterans Affairs, Eastern Colorado Health Care System, Denver, CO, USA;Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-5688, USA

关键词: Emphysema;    COPD pathology;    Airway epithelium;    Viral infection;    COPD exacerbation;   

Others  :  790696
DOI  :  10.1186/1465-9921-15-11

 received in 2013-12-02, accepted in 2014-02-03,  发布年份 2014

【 摘 要 】

Background

Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD.

Methods

C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV).

Results

Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.

Conclusions

These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.

【 授权许可】

   
2014 Ganesan et al.; licensee BioMed Central Ltd.

【 图 表 】

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