Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia.

K. Kobayashi, Matthias A Salathe, M. M. Pratt, N. J. Cartagena, F. Soloni, Z. V. Seybold, Adam Wanner

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Abstract

To study the effect of the inflammatory mediator hydrogen peroxide (H2O2) on airway ciliary activity, we measured ciliary beat frequency (CBF) in cultured tracheal explants from sheep. Addition of H2O2 (10(-8) to 10(-4) M) produced a concentration-dependent mean (+/- SEM) decrease in CBF between 11.1 +/- 0.4% (P less than 0.01) and 100 +/- 0% (P less than 0.001); at each concentration, the maximal effect was reached by 20 to 25 min. Between 10(-8) and 10(-6) M H2O2, the decrease in CBF was reversible, lactate dehydrogenase (LDH) release was not significantly increased, and major morphologic lesions were not seen. At higher concentrations of H2O2, incomplete recovery of CBF (10(-5) M) or irreversible ciliostasis (10(-4) M) developed, and a significant increase in LDH and morphologic lesions were present. Catalase (2,000 U/ml) and H-7 (10(-5) M), a protein kinase inhibitor, abolished cilioinhibition produced by H2O2 at 10(-6) M and lower concentrations but not at 10(-5) M and higher concentrations. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, caused a dose-dependent (10(-11) to 10(-5) M), reversible decrease in CBF; this effect was abolished by H-7. We suggest that at nonlethal concentrations, H2O2 inhibits the beat frequency of airway epithelial cilia reversibly, through the activation of second messengers, including protein kinase C. This mechanism might contribute to the previously demonstrated impairment of mucociliary clearance in airway inflammation.

Original languageEnglish
Pages (from-to)667-673
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume6
Issue number6
StatePublished - Jun 1 1992

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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Cilia
L-Lactate Dehydrogenase
Protein Kinase C
Hydrogen Peroxide
Sheep
Mucociliary Clearance
Bridge clearances
Second Messenger Systems
Protein Kinase Inhibitors
Catalase
Acetates
Inflammation
Chemical activation
Recovery
Scanning electron microscopy
phorbol-12-myristate

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Kobayashi, K., Salathe, M. A., Pratt, M. M., Cartagena, N. J., Soloni, F., Seybold, Z. V., & Wanner, A. (1992). Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia. American Journal of Respiratory Cell and Molecular Biology, 6(6), 667-673.

Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia. / Kobayashi, K.; Salathe, Matthias A; Pratt, M. M.; Cartagena, N. J.; Soloni, F.; Seybold, Z. V.; Wanner, Adam.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 6, No. 6, 01.06.1992, p. 667-673.

Research output: Contribution to journalArticle

Kobayashi, K, Salathe, MA, Pratt, MM, Cartagena, NJ, Soloni, F, Seybold, ZV & Wanner, A 1992, 'Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia.', American Journal of Respiratory Cell and Molecular Biology, vol. 6, no. 6, pp. 667-673.
Kobayashi K, Salathe MA, Pratt MM, Cartagena NJ, Soloni F, Seybold ZV et al. Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia. American Journal of Respiratory Cell and Molecular Biology. 1992 Jun 1;6(6):667-673.
Kobayashi, K. ; Salathe, Matthias A ; Pratt, M. M. ; Cartagena, N. J. ; Soloni, F. ; Seybold, Z. V. ; Wanner, Adam. / Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia. In: American Journal of Respiratory Cell and Molecular Biology. 1992 ; Vol. 6, No. 6. pp. 667-673.
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