Abstract

Exposure to cigarette smoke is associated with airway epithelial mucus cell hyperplasia and a decrease in cilia and ciliated cells. Few models have addressed the long-term effects of chronic cigarette smoke exposure on ciliated epithelial cells. Our previous in vitro studies showed that cigarette smoke decreases ciliary beat frequency (CBF) via the activation of protein kinase C (PKC). We hypothesized that chronic cigarette smoke exposure in an in vivo model would decrease airway epithelial cell ciliary beating in a PKC-dependent manner. We exposed C57BL/6 mice to whole-body cigarette smoke 2 hours/day, 5 days/week for up to 1 year. Tracheal epithelial cell CBF and the number of motile cells were measured after necropsy in cut tracheal rings, using high-speed digital video microscopy. Tracheal epithelial PKC was assayed according to direct kinase activity. At 6 weeks and 3 months of smoke exposure, the baseline CBF was slightly elevated (∼1 Hz) versus control mice, with no change in β-agonist-stimulated CBF between control mice and cigarette smoke-exposed mice. By 6 months of smoke exposure, the baseline CBF was significantly decreased (2-3 Hz) versus control mice, and a β-agonist failed to stimulate increased CBF. The loss of β-agonist-increased CBF continued at 9 months and 12 months of smoke exposure, and the baseline CBF was significantly decreased to less than one third of the control rate. In addition to CBF, ciliated cell numbers significantly decreased in response to smoke over time, with a significant loss of tracheal ciliated cells occurring between 6 and 12 months. In parallel with the slowing of CBF, significant PKC activation from cytosol to the membrane of tracheal epithelial cells was detected in mice exposed to smoke for 6-12 months.

Original languageEnglish (US)
Pages (from-to)635-640
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume43
Issue number6
DOIs
StatePublished - Dec 1 2010

Fingerprint

Smoke
Tobacco Products
Epithelial Cells
Protein Kinase C
Cell Count
Chemical activation
Video Microscopy
Cilia
Mucus
Inbred C57BL Mouse
Cytosol
Hyperplasia
Microscopic examination
Phosphotransferases
Membranes

Keywords

  • Chronic cigarette smoke
  • Cilia
  • PKC

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Long-term cigarette smoke exposure in a mouse model of ciliated epithelial cell function. / Simet Chadwick, Samantha M; Sisson, Joseph Harold; Pavlik, Jacqueline A.; DeVasure, Jane M.; Boyer, Craig; Liu, Xiang-de; Kawasaki, Shin; Sharp, John G; Rennard, Stephen I.; Wyatt, Todd A.

In: American journal of respiratory cell and molecular biology, Vol. 43, No. 6, 01.12.2010, p. 635-640.

Research output: Contribution to journalArticle

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abstract = "Exposure to cigarette smoke is associated with airway epithelial mucus cell hyperplasia and a decrease in cilia and ciliated cells. Few models have addressed the long-term effects of chronic cigarette smoke exposure on ciliated epithelial cells. Our previous in vitro studies showed that cigarette smoke decreases ciliary beat frequency (CBF) via the activation of protein kinase C (PKC). We hypothesized that chronic cigarette smoke exposure in an in vivo model would decrease airway epithelial cell ciliary beating in a PKC-dependent manner. We exposed C57BL/6 mice to whole-body cigarette smoke 2 hours/day, 5 days/week for up to 1 year. Tracheal epithelial cell CBF and the number of motile cells were measured after necropsy in cut tracheal rings, using high-speed digital video microscopy. Tracheal epithelial PKC was assayed according to direct kinase activity. At 6 weeks and 3 months of smoke exposure, the baseline CBF was slightly elevated (∼1 Hz) versus control mice, with no change in β-agonist-stimulated CBF between control mice and cigarette smoke-exposed mice. By 6 months of smoke exposure, the baseline CBF was significantly decreased (2-3 Hz) versus control mice, and a β-agonist failed to stimulate increased CBF. The loss of β-agonist-increased CBF continued at 9 months and 12 months of smoke exposure, and the baseline CBF was significantly decreased to less than one third of the control rate. In addition to CBF, ciliated cell numbers significantly decreased in response to smoke over time, with a significant loss of tracheal ciliated cells occurring between 6 and 12 months. In parallel with the slowing of CBF, significant PKC activation from cytosol to the membrane of tracheal epithelial cells was detected in mice exposed to smoke for 6-12 months.",
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AU - Simet Chadwick, Samantha M

AU - Sisson, Joseph Harold

AU - Pavlik, Jacqueline A.

AU - DeVasure, Jane M.

AU - Boyer, Craig

AU - Liu, Xiang-de

AU - Kawasaki, Shin

AU - Sharp, John G

AU - Rennard, Stephen I.

AU - Wyatt, Todd A

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