Biomedical Engineering Reference
In-Depth Information
reduction in an undefined ''peroxynitrite inhibitory activity'' in sputum of
COPD patients (42). Peroxynitrite reacts with tyrosine residues in certain
proteins to form 3-nitrotyrosine, which may be detected immunologically.
There is an increased 3-nitrotyrosine immunoreactivity in sputum macro-
phages from patients with COPD (35). Oxidative stress and peroxynitrite
may also reduce histone deacetylase-2 levels in macrophages, thereby indu-
cing resistance to the anti-inflammatory actions of corticosteroids (43).
IV. PEPTIDE MEDIATORS
A.
Endothelins
There is an increased concentration of endothelin-1 (ET-1) in induced
sputum of patients with COPD (44), particularly during exacerbations
(45). Plasma ET-1 concetnrations are also elevated in COPD patients, par-
ticularly in patients who develop nocturnal hypoxemia during the night
(46,47). This may reflect the release of ET-1 by hypoxemia. The ET-1 is a
potent vasoconstrictor and also causes vascular smooth muscle hyperplasia.
There is increased expression of ET-1 in pulmonary endothelial cells of
patients with COPD who have secondary pulmonary hypertension (48),
suggesting that ET-1 may contribute to the vascular remodeling associated
with hypoxic pulmonary hypertension.
B. Bradykinin
Although the role of bradykinin and related kinins in asthma has been
extensively explored (49), there is very little information about kinins in
COPD. It is likely that kinins are generated in the airway of COPD patients
as plasma exudation occurs. Furthermore, proinflammatory cytokines that
are found in COPD airways increase the expression of bradykinin B
1
-and
B
2
-receptors in pulmonary cells (50-52). Bradykinin is a potent bronchocon-
strictor of human airways, particularly small airways (53), stimulates mucus
secretion (54), and potently potentiates cough by an effect on unmyelinated
sensory nerve endings in the airways (55).
C. Tachykinins
Increased substance P concentrations have been reported in induced sputum
of patients with chronic bronchitis (56); this is presumably derived form sen-
sory nerve endings, although non-neuronal sources of tachykinins are now
recognized. For example, sputum macrophages express substance P in
response to endotoxin stimulation (57). Tachykinins are potent stimulants
of submucosal gland and goblet cell secretion. The effects of cigarette smoke
on mucus secretion is also blocked by tachykinin antagonists in experimen-
tal animals, indicating that tachykinin release from sensory nerves mediates
