PuSH - Publication Server of Helmholtz Zentrum München

Cigarette smoke causes acute airways disease and exacerbates chronic obstructive lung disease in neonatal mice.

Am. J. Physiol. Lung Cell Mol. Physiol. 311, L602-L610 (2016)
Postprint DOI
Open Access Green
as soon as is submitted to ZB.
Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS)-exposure and increased respiratory morbidity in young children. However, how CS induces early onset airways disease in young children and how it interacts with endogenous risk factors remains poorly understood. We, therefore exposed 10 day old neonatal wild-type and βENaC-transgenic mice with cystic fibrosis like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the BALF which was accompanied by increased levels of Mmp12 and Cxcl1. BALF from βENaC-transgenic mice contained greater numbers of macrophages which did not increase following acute CS-exposure, however there was significant increase in airway neutrophilia compared to filtered air transgenic and CS-exposed wild-type controls. Interestingly, wild-type and βENaC-transgenic mice demonstrated epithelial airway and vascular remodeling following CS-exposure. Morphometric analysis of lung sections revealed that CS-exposure caused increased mucus accumulation in the airway lumen of neonatal βENaC-transgenic mice compared to wild-type controls, which was accompanied by an increase in the number of goblet cells and Muc5ac upregulation. We conclude that short-term CS exposure i) induces acute airways disease with airway epithelial and vascular remodeling in neonatal wild-type mice; and ii) exacerbates airway inflammation, mucus hypersecretion and mucus plugging in neonatal βENaC-transgenic mice with chronic lung disease. Our results in neonatal mice suggest that young children may be highly susceptible to develop airways disease in response to tobacco smoke exposure and that adverse effects may be aggravated in children with underlying chronic lung diseases.
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Airways Disease ; Cigarette Smoke ; Inflammation ; Mucus ; Newborn; Channel-overexpressing Mice; Cystic-fibrosis; Chronic-bronchitis; Pulmonary-disease; Induced Emphysema; Flow Limitation; Exposed Mice; Inflammation; Elastase; Mucus
Reviewing status
Institute(s) Institute of Lung Biology (ILBD)
German Center for Lung Research (DZL)