Biomedical Engineering Reference
In-Depth Information
B. Circulating Inflammatory Cells
Patients with COPD characteristically show increased number of circulating
neutrophils. Besides, several studies have now clearly identified potentially
relevant functional abnormalities of these cells in COPD. These include:
(a) enhanced chemotaxis and extracellular proteolysis (10); (b) a higher
capacity to produce ROS, respiratory burst (11); (c) increased surface
expression of several adhesion molecules, particularly Mac-1 (CD11b)
(12). Interestingly, this persisted during the process of apoptosis in vitro
(13), an observation that can be relevant for neutrophil clearance by macro-
phages from inflamed tissues; and (d) down-regulation of one type of G-pro-
tein subunit (Gas) involved in the intracellular signal transduction pathway
of a variety of cellular processes including CD11b expression (12) and the
control of the intracellular vesicular trafficking (14). The latter is required
for the activation of NADPH oxidase, the enzyme which is eventually
responsible of the respiratory burst in neutrophils (11).
Although circulating lymphocytes have been less studied than circulating
neutrophils in COPD, there are also some hints of abnormal lymphocyte func-
tion in these patients. For instance, Sauleda et al. (15) showed that the activity
of cytochrome oxidase, the terminal enzyme in the mitochondrial electron
transport chain, was increased in circulating lymphocytes of COPD patients.
This abnormality could be detected also in patients with other chronic inflam-
matory diseases, both of pulmonary—bronchial asthma—and nonpulmonary
origin—chronic arthritis—suggesting that it may be a nonspecific marker of
lymphocyte activation in chronic inflammatory diseases (15).
Finally, peripheral monocytes seem also to function abnormally in
patients with COPD because they produce increased quantities of TNF
a
when stimulated in vitro (16). This is particularly evident in patients with
COPD and low body weight, suggesting that an excessive production of
TNF
a
by peripheral monocytes may play a role in the pathogenesis of
weight loss in COPD (16) (see below).
C.
Increased Plasma Levels of Proinflammatory Cytokines
Numerous studies have now reported increased levels of circulating cyto-
kines and acute phase reactants in the peripheral circulation of patients with
COPD, including TNF
a
, its receptors (TNFR-55 and TNFR-75), IL-6, IL-
8, C-reactive protein, LPS-binding protein, Fas and Fas-L (17-20). These
abnormalities were seen in patients considered clinically stable but were
generally more pronounced during exacerbations of the disease (19).
D. Mechanisms of Systemic Inflammation in COPD
To date, the precise mechanism(s) underlying systemic inflammation in
COPD has not been identified. Several not mutually exclusive candidates
