Toxicology Letters 96,97 (1998) 245 – 251
Defense and repair mechanisms in the airway epithelium
exposed to oxidative stress
Effects of analogues of retinoic acid
Armelle Baeza-Squiban *, Emmanuelle Boisvieux-Ulrich, Laure Delcher,
Francelyne Marano
Laboratoire de Cytophysiologie et Toxicologie cellulaire, Uniersite ´ Paris 7, Denis Diderot, tour 53 -54, 3 e ´tage, case 7073,
2 place jussieu, 75 251 Paris ce ´dex 05, France
Abstract
A model of rabbit tracheal epithelial (RTE) cells in vitro was developed in order to investigate the effects, on the
airway epithelium, of reactive oxygen species (ROS) generated by H
2
O
2
in association or not in association with
Fe
2 +
. The immediate consequence of a 24 h exposure of RTE cells to an oxidative stress was an increase in catalase
activity whereas superoxide dismutase activity was not modified. A latter consequence of a chronic ROS insult was
the induction of a repair mechanism which led to squamous metaplasia (SM). SM is characterized by a stratification
of the epithelium, the expression of the cytokeratin 13 and the appearance of cells with cross-linked envelopes.
Reversible modifications between mucociliary and squamous phenotype are modulated by retinoids. The action of
retinoids is selective: metaplasia is inhibited by agonists of RAR and receptors and not by an agonist of RAR
receptors. © 1998 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Tracheal epithelium; Oxidative stress; Squamous metaplasia; Anti-oxidant enzymes; Retinoids
1. Introduction
The respiratory tract is continually exposed to
air pollutants which are frequently present in
urban atmosphere. Epidemiological studies have
demonstrated that environmental pollution is im-
plicated in the maintenance and/or aggravation of
pre-existing respiratory diseases. Many atmo-
spheric pollutants are oxidants as O
3
, NO
2
, SO
2
,
some mineral particles and components of
cigarette smoke (Weitzman and Graceffa, 1984;
Schlesinger, 1989; Mossman et al., 1990; Guil-
ianelli et al., 1993; Chitano et al., 1995). In addi-
tion to their oxidative properties, these pollutants
may secondarily activate macrophages and neu-
trophiles to release reactive oxygen species (ROS)
(Barnes, 1990). In vivo studies have not clarified
* Corresponding author. Tel.: +33 01 44276062; fax: +33
01 44276999; e-mail: Marano@paris7.jussieu.fr
0378-4274/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved.
PII S0378-4274(98)00079-4