Author
Elliott, Margaret | |
SISSON, JOSEPH - UNIV OF NE MEDICAL CNTR | |
WYATT, TODD - UNIV OF NE MEDICAL CNTR |
Submitted to: American Journal of Respiratory Cell and Molecular Biology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/18/2006 Publication Date: 11/1/2006 Citation: Elliott, M., Sisson, J.H., Wyatt, T.A. 2006. Effects of Cigarette Smoke and Alcohol on Ciliated Tracheal Epithelium and Inflammatory Cell Recruitment. American Journal of Respiratory Cell and Molecular Biology. 36(4):452-9. Interpretive Summary: The ciliated epithelium is the first line of host defense against infection of the lung. The majority of alcoholics are smokers who are at a high risk for developing lung infections. The combined effect of smoke and alcohol exposure on the upper airway and immune cell populations in the lung has not yet been studied in vivo. In this study, we exposed mice to alcohol, cigarette smoke or a combination of both. The effects of such exposures on bronchoalveolar lavage (BAL) cell populations, ciliary beat frequency (CBF), and airway kinase activity were measured. We found that total BAL cell numbers decrease with alcohol exposure alone and increase with smoke exposure alone. Concurrent smoke and alcohol resulted in BAL cell numbers similar to that of smoke alone. Baseline CBF was not affected by any treatment, however isoproterenol stimulation of CBF was blunted by alcohol exposure and actually slowed below baseline with combined smoke and alcohol exposure. Isoproterenol-induced cAMP-dependent protein kinase (PKA) activity was inhibited with alcohol exposure independent of smoke exposure. Smoke exposure activated protein kinase C (PKC) independent of alcohol exposure. The isoproterenol-induced slowing below baseline of CBF following combined smoke and alcohol exposure demonstrates a novel ciliary impairment likely related to the combination of alcohol-mediated PKA desensitization and smoke-stimulated PKC activation. This may contribute to increased pulmonary infection rates in those who smoke and drink heavily. Technical Abstract: The ciliated epithelium is the first line of host defense against infection of the lung. The majority of alcoholics are smokers who are at a high risk for developing lung infections. Previously, we reported the effects of cigarette smoke and alcohol exposure on ciliary beat frequency (CBF), cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in bovine bronchial epithelial cells (BBEC) in vitro. The combined effect of smoke and alcohol exposure on the murine ciliated tracheal epithelium has not yet been studied in vivo. We hypothesized that the effects of smoke and alcohol exposure that we observed in vitro could be recapitulated in vivo. To test this hypothesis, we exposed female C57BL/6 mice (n=11-12/group) to whole body cigarette smoke only, 20% alcohol only (in drinking water), or the combination of cigarette smoke plus 20% alcohol for 6 weeks. Appropriate sham exposure controls were also evaluated. Effects of such exposures on bronchoalveolar lavage (BAL) cell populations, CBF, and airway kinase activity were assessed. We found that total BAL cells were decreased in animals exposed to alcohol alone and increased in animals exposed to smoke alone. Mice receiving concurrent smoke and alcohol had cell levels similar to that of smoke alone. Baseline CBF was not affected in any group, however isoproterenol stimulation of CBF was blunted by alcohol exposure and actually slowed below baseline in the smoke + alcohol group. Isoproterenol-induced PKA activity was inhibited in mice receiving alcohol independent of smoke exposure. Smoke exposure activated PKC independent of alcohol exposure. These in vivo findings recapitulate the in vitro effects of cigarette smoke and alcohol on the ciliated airway epithelium. The isoproterenol-induced slowing below baseline of CBF following combined smoke + alcohol exposure demonstrates a novel ciliary impairment likely related to the combination of alcohol-mediated PKA desensitization and smoke-stimulated PKC activation. |