Reactive oxygen species provoke secretion of mucin and activate
phospholipase c in airway epithelial cells in vitro via a mechanism
dependent on nitric oxide.
Wright, David T., Bernard M. Fischer, Chengming Li, Lori G. Rochelle,
Nancy J. Akley, and Kenneth B. Adler.
Department of Toxicology, Department of Anatomy, Physiological
Sciences, and Radiology, College of Veterinary Medicine, North
Carolina State University, Raleigh, North Carolina
APStracts 3:0120L, 1996.
Reactive oxygen species (ROS) have been implicated in the pathogenesis
of a wide variety of respiratory diseases. We investigated mechanisms
of ROS - induced mucin secretion by guinea pig tracheal epithelial
(GPTE) cells in primary culture, and ROS - induced activation of the
second messenger - producing enzyme, phospholipase C (PLC), in GPTE
cells and in a virally-transformed cell line (BEAS-2B) derived from
human bronchial epithelium. Mucin secretion was measured by a
monoclonal antibody - based ELISA, and PLC activation was assessed by
anion exchange chromatography. ROS generated enzymatically by
xanthine oxidase in the presence of purine (P+XO; 500 [mu]M + 20
mU/ml) enhanced release of mucin by GPTE cells and activated PLC in
GPTE and BEAS cells. Hypersecretion of mucin and activation of PLC in
response to P+XO appeared to occur via an intracellular pathway(s)
dependent on endogenously produced nitric oxide (NO) and possibly
intracellularly generated oxidants. Both responses could be blocked
or attenuated by preincubation of the cells with NG-monomethyl-L
-arginine (L-NMA), an inhibitor of the enzyme nitric oxide synthase
(NOS), or with dimethylthiourea (DMTU) a compound that can react with
a variety of intracellular oxidant species. Reactive nitrogen species
(RNS) generated chemically also stimulated secretion of mucin and
activated PLC via a mechanism dependent (at least in part) on
intracellular oxidant-mediated process(es). The results suggest that
intracellularly - generated radical species of nitrogen and oxygen
may be important modulators of the response of airway epithelial
cells to external oxidant stress.
Received 5 October 1995; accepted in final form 10 July 1996.
APS Manuscript Number L295-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996