Biomedical Engineering Reference
In-Depth Information
(BAL) from patients with COPD has also been shown to contain increased
levels of eosinophilic cationic protein. Furthermore, peripheral blood eosi-
nophilia is also considered to be a risk factor for the development of airway
obstruction in patients with chronic bronchitis and is an adverse prognostic
sign. However, despite the presence of increased number of eosinophils,
EPO-mediated generation of specific 3-bromotyrosine has not been detected
in COPD patients. This does not provide support for a role of brominating
oxidants in eosinophil-mediated ROS damage COPD.
VI. ALTERATIONS IN LUNG TISSUE
An important link between oxidative stress and the pathogenesis of COPD
would come from the demonstration of the reaction of ROS with target lung
molecules and the presence of these oxidatively modified molecules in
increased amounts in the lungs of smokers, particularly those who develop
COPD. ROS such as O
2
-
and
OH, generated and released by activated
immune and inflammatory cells, are highly reactive, and when generated
close to cell membranes oxidize membrane phospholipids (lipid peroxida-
tion), a process which may continue as a chain reaction (Fig. 7). Thus, a
single
OH can result in the formation of many molecules of lipid hydroper-
oxides in the cell membrane. Many of the effects of ROS in airways may be
mediated by the secondary release of inflammatory lipid mediators such
as 4-hydroxy-2-nonenal (4-HNE), a footprint of oxidative stress
=
lipid
peroxidation. 4-HNE, a highly reactive diffusible end product of lipid
Figure 7
Membrane lipid peroxidation of polyunsaturated fatty acids leading to
generation of various aldehydes.
