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A1096
October 15, 2012
1:00:00 PM - 4:00:00 PM
Room Hall C-Area K
Effect of Cigarette Smoke on Immature Human Airway Smooth Muscle
Elizabeth Vogel, M.D., Sarah K. VanOosten, B.S., Michelle A. Holman, B.S., Michael A. Thompson, B.S., Y. S. Prakash, M.D.,Ph.D., Christina M. Pabelick, M.D.
Mayo Clinic, Rochester, Minnesota, United States
Background:

Premature infants are at increased risk of developing bronchopulmonary dysplasia (BPD) and future airway hyperreactivity due to frequent exposure to mechanical ventilation and supplemental oxygen (hyperoxia). Environmental tobacco smoke exposure may further exacerbate airway hyperreactivity. Airway hyperreactivity involves increased intracellular Ca2+ ([Ca2+]i), increased contractility, and airway smooth muscle (ASM) hyperplasia. Current data from our lab and others has shown that plasma membrane invaginations, termed caveolae, play an important role in ASM regulation through interference with [Ca2+]i regulation leading to increased contractility and proliferation. In this study, using fetal ASM (fASM) cells, we explored the effect of cigarette smoke exposure on caveolar regulation of [Ca2+]i, ASM cell proliferation and apoptosis.

Methods:

Fetal ASM cells (18-22 weeks PCA; de-identified samples, IRB exempt) were exposed to 0.5, 1, or 1.5% cigarette smoke extract (CSE) for 18-24 hours. Western blot analysis was used to determine the level of caveolar, apoptotic, and proliferative protein expression. fASM cells (control and CSE-exposed) were loaded with Fluo-4, a fluorescent Ca2+ indicator dye, to investigate the effects of CSE on agonist-induced [Ca2+]i responses.

Results:

Exposure of fASM cells to CSE (0.5 to 1.5%) resulted in a significantly increased expression of caveolar proteins caveolin-1, caveolin-2, cavin-1, cavin-3, and cavin-4, compared to control. CSE exposure also increased [Ca2+]i responses to agonist histamine (10µM). However, the effects of CSE were not concentration-dependent. Apoptotic markers Cytochrome C and Caspase-9 were increased in cells exposed to higher concentrations of CSE (1.5%), while exposure to lower concentrations (0.5 and 1%) increased expression of proliferative markers p27 and PCNA.

Conclusion:

These results demonstrate that cigarette smoke exposure causes its detrimental effects, at least in part, through modulation of caveolar signaling in developing ASM. Increased expression of caveolar proteins results in enhanced [Ca2+]i response to agonists thereby increasing airway contractility. In addition, CSE exposure leads to a shift in the balance between proliferation and apoptosis. All these results indicate that environmental tobacco smoke contributes to increased airway hyperreactivity in premature children

Copyright © 2012 American Society of Anesthesiologists