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Figure 9 (a) Photographs from immunostaining for 4-HNE in lung tissue from
subjects with and without COPD. 4-HNE adducts were localized predominantly in
bronchial, bronchiolar, and alveolar epithelial cells, in endothelial cells, neutrophils,
and CD68 þ cells (macrophages) (19). The levels of 4-HNE-modified proteins were
higher in bronchial and alveolar epithelial cells, and bronchial endothelial cells
and neutrophils of subjects with COPD compared to subjects without COPD 1A:
Non-COPD, bronchial; IB: Non-COPD, alveolar; 2A: COPD bronchial; 2B: COPD
alveolar. L ¼ lumen. Original magnification: 200 . (b) Individual immunostaining
scores for 4-HNE-adducts in bronchial (br) and alveolar (alv) lung tissue in epithelial
cells, endothelial cells, and neutrophils. The mean is indicated, as well significance
levels (p) for differences between the indicated groups.
oxidative stress in the blood in patients with COPD. The neutrophil appears
to be a critical cell in the pathogenesis of COPD (1). Epidemiological studies
have shown a relationship between circulating neutrophil numbers and the
FEV 1 . Moreover, a relationship has also been shown between the change in
peripheral blood neutrophil count and the change in airflow limitation over
time. Similarly, a correlation between O 2 - release by peripheral blood
neutrophils and bronchial hyperreactivity in patients with COPD has been
shown, suggesting a role for systemic ROS in the pathogenesis of the airway
abnormalities in COPD (21).
Various studies have demonstrated increased production of O 2 - from
peripheral blood neutrophils obtained from patients during acute exacerba-
tions of COPD, which returned to normal when the patients were clinically
stable (12,22). Other studies have shown that circulating neutrophils from
patients with COPD show upregulation of their surface adhesion molecules,
which may also be an oxidant-mediated effect (12,23). Activation may
be even more pronounced in neutrophils which are sequestered in the
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