Oxidative Stress - Chronic Obstructive Pulmonary Disease - page 297

GSH in chronic smokers may not be sufficient to deal with the excessive oxi-
dant burden during smoking, when acute depletion of GSH may occur (44).
Neurohr et al. (47) recently showed that decreased GSH levels in BALF cells
of chronic smokers were associated with a decreased expression of g -GCS-
light subunit without a change in g -GCS-heavy subunit expression. This high-
lighted the fact that increased GSH levels in the ELF of chronic smokers were
not associated with increased GSH levels in alveolar macrophages. The acute
effects of cigarette smoke condensate (CSC) on GSH metabolism have been
studied in a human alveolar epithelial cell line in vitro, and in rat lungs in
vivo after intra-tracheal CSC instillation, CSC produced a dose and time-
dependent depletion of intracellular GSH, concomitant to the formation of
GSH-conjugates. Similar results were shown in animal lungs in vivo (2,44).
Thus, further studies are needed to investigate the regulation of GSH levels
in the lungs of smokers and patients with COPD to devise appropriate GSH
therapy.
XI. AIRSPACE EPITHELIAL INJURY = PERMEABILITY
By virtue of its direct contact with the environment, the airspace epithelial
surface of the lungs is particularly vulnerable to the effects of oxidative
stress produced by cigarette smoke. Cigarette smoke-induced oxidant injury
to the respiratory tract epithelial cells may result from several processes e.g.,
(a) a direct toxic interaction with constituents of cigarette smoke (including
free radicals) which have penetrated the protective antioxidant shield of the
ELF; (b) damage to the cells by toxic reactive products generated by inter-
action between cigarette smoke and ELFs; and (c) reactions occurring sub-
sequent to activation of inflammatory-immune processes initiated by (a)
and = or (b).
Oxidants in cigarette smoke can produce direct oxidative damage to
components of the lung matrix, such as elastin and collagen. Elastin synth-
esis and repair can also be impaired by cigarette smoke, which can augment
proteolytic damage to matrix components and thus enhance the develop-
ment of emphysema.
Airspace epithelial injury is an important early consequence of the
inflammation produced by cigarette smoke and results in an increase in air-
space epithelial permeability. Human studies have shown increased epithelial
permeability in chronic smokers compared with non-smokers, as measured
by increased 99m technetium-diethylenetriaminepentacetate ( 99m Tc-DTPA)
lung clearance, with a further increase in 99m Tc-DTPA clearance following
acute smoking (14). The injurious effect of both the whole and vapor phases
of cigarette smoke on human alveolar epithelial cell monolayers is shown by
increased epithelial cell detachment, decreased cell adherence, and increased
cell lysis (2). These effects were in part oxidant-mediated since they were