A low vitamin a status increases the susceptibility to cigarette smoke-induced lung emphysema in c57bl/6j mice

Chronic obstructive pulmonary disease (copd) is characterized by chronic airway inflammation. cigarette smoke hasbeen considered a major player in the pathogenesis of copd. the inflamed airways of copd patients contain severalinflammatory cells. vitamin a metabolites have been implicated in the repair of lung damage. exposure to cigarettesmoke has been shown to depress levels of retinol in lungs of rats. the purpose of this study was to investigate if a low,but not deficient,vitamin a status potentiated susceptibility to the development of cigarette smoke-induced lungemphysema in mice. mice were bred that were the offspring's of 3 generations of mice that were fed a purified dietcontaining low levels of vitamin a and exposed to cigarette smoke for 3 months,every weekday. then,levels of 9-cis,13-cis,and all-trans retinoic acid,retinol and retinyl palmitate were measured in plasma,liver and right lung lobe. theleft lung lobe was used to assess mean linear intercept (lm),as a measure of smoke-induced lung damage. average feedintakes were not different between treatment groups. we show that both retinol and retinyl palmitate levels weredramatically decreased in the storage organs of mice on the low vitamin a diet (retinol 2-fold in both lung and liver,andretinyl palmitate 5- fold in lung) which shows that the depletion was successful. however,this treatment did not resultin the development of lung emphysema. however,smoke exposure led to a significant increase in lm in mice with alow vitamin a status compared to the room air-breathing controls. lung levels of acid retinoids were similar in all mice,irrespective of diet or smoke exposure. concluding,a low vitamin a status increases the susceptibility to thedevelopment of cigarette smoke-induced lung emphysema,possibly because of decreased anti-oxidant capacity in thelungs due to locally reduced retinol and retinyl palmitate levels. these observations indicate that human populationswith a low vitamin a status and a high prevalence of smoking may be at increased risk of developing lung emphysema.