AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 596-L600, Copyright © 1995 by American Physiological Society
Ethanol stimulates apparent nitric oxide-dependent ciliary beat frequency in bovine airway epithelial cells
J. H. Sisson
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198, USA.
The mucociliary apparatus of the lung provides an important host-defense
function by clearing the upper airway of inhaled particles and infectious
microorganisms. Because lung host defenses are impaired in alcoholics, we
hypothesized that ethanol would decrease ciliary motility in airway
epithelium. Ciliary beat frequency (CBF) was measured by videomicroscopy in
primary cultures of ciliated bovine bronchial epithelial cells (BBECs).
Ethanol rapidly stimulated ciliary motility in a time-dependent fashion
with concentrations as low as 10 mM. No detectable decreases in ciliary
motility were noted until ethanol concentrations exceeded 1,000 mM. Because
many substances stimulate ciliary motility by releasing nitric oxide (NO)
via upregulation of nitric oxide synthase (NOS), we preincubated ciliated
BBECs with a stereospecific NOS inhibitor, NG-monomethyl-L-arginine
(L-NMMA). L-NMMA completely blocked ethanol-induced stimulation of CBF,
which could be subsequently restored by adding either L-arginine or sodium
nitroprusside, which is a direct NO donor. These results indicate that
ethanol, at clinically relevant concentrations, stimulates the release of
NO by airway epithelium that upregulates ciliary motility. The rapidity of
this response suggests upregulation of the constitutive NOS, known to be
present in airway epithelium, and may explain the increases in mucociliary
clearance observed in previous studies of ethanol ingestion in animals and
in humans. These data also suggest a novel signal transduction pathway, the
NO/NOS system, by which ethanol may exert some of its diverse biologic
effects.
