Published ahead of print on November 1, 2006, doi:10.1165/rcmb.2005-0440OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 4, April 2007, 452-459 A more recent version of this article appeared on April 1, 2007
Submitted on November 29, 2005 Effects of Cigarette Smoke and Alcohol on Ciliated Tracheal Epithelium and Inflammatory Cell RecruitmentMargaret K Elliott1,1 Pulmonary, Critical Care, Sleep and Allergy Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA, 2 Pulmonary, Critical Care, Sleep and Allergy Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Veterans Affairs Medical Center Research Service, Omaha, NE, USA * To whom correspondence should be addressed. E-mail: twyatt{at}unmc.edu.
Ciliated epithelium represents the first line of host defense against lung infection. Most alcoholics smoke and are at high risk for developing lung infections. We reported that cigarette smoke activates protein kinase C (PKC) and alcohol desensitizes ciliary beat frequency (CBF) to beta-agonists in bovine bronchial epithelial cells in vitro. The combined effect of smoke and alcohol exposure on mouse ciliated tracheal epithelium has not been studied in vivo. We hypothesized that previously observed in vitro effects of smoke and alcohol exposure could be replicated in vivo. Female C57BL/6 mice were exposed to whole body cigarette smoke only, 20% alcohol ad libitum in drinking water only, or the combination of cigarette smoke plus alcohol for 6 weeks. Bronchoalveolar lavage (BAL) cell populations, CBF, and airway kinase activity were assessed. Total BAL cells were decreased in animals exposed to alcohol alone and increased in animals exposed to smoke alone. Mice receiving smoke and alcohol had cell levels similar to 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 activated PKC independent of alcohol. 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 possibly through acetaldehyde present in the vapor phase of cigarette smoke.
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