Effects of cigarette smoke extract and nicotine on bronchial tone and acetylcholine-induced airway contraction in mouse lung slices.
BACKGROUND
Tobacco smoke is a key risk factor for chronic obstructive pulmonary disease, but it may also alter the pathophysiology of asthma. In the present study, we analyzed whether tobacco smoke has acute or chronic effects on bronchial tone and whether it alters bronchial reactivity in vitro.


METHODS
Airways in murine lung slices were digitally recorded and the change in cross-sectional area with time was quantified. T-bet KO mice served as a model for bronchial hyperreactivity. T-bet KO mice show a shift towards type 2 helper T lymphocytes and display histological as well as functional characteristics of asthma. Cigarette smoke extract (CSE) was obtained using commercially available cigarettes (Gauloise Blondes) by drawing cigarette smoke slowly through a water pump into a tube containing 10 mL of DMEM culture medium.


RESULTS
Acute exposure to CSE led to relaxation of the airway. Acute exposure to nicotine resulted in a minor relaxation of the airway in Balb/C mice and in nonsignificant relaxation of the airway in T-bet KO mice. The nicotinic acetylcholine-receptor hexamethonium partially inhibited CSE-induced airway relaxation. Airway contraction in response to acetylcholine was stronger in T-bet KO mice than in Balb/C mice. After exposure to CSE or nicotine for 48 hours, acetylcholine-induced airway contraction was no longer different between the 2 types of mice.


CONCLUSIONS
Our data indicate that acute exposure to CSE leads to airway relaxation, which is partially mediated by nicotine. Chronic exposure to CSE reverses bronchial hyperreactivity in the airways of T-bet KO mice; this effect can be mimicked by chronic exposure to nicotine.
Streck
E
E
Department of Thoracic Medicine, Medizinische Klinik-Innenstadt, Ludwig-Maximilians-University, Munich, Germany.
Jörres
R A
RA
Huber
R M
RM
Bergner
A
A
D000109:Acetylcholine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics; D001986:Bronchial Spasm / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D045424:Complex Mixtures / Q000008:administration & dosage* / Q000009:adverse effects; D018738:Hexamethonium / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology; D009924:Organ Culture Techniques; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D045424:Complex Mixtures; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018738:Hexamethonium; D009538:Nicotine; D000109:Acetylcholine