Biomedical Engineering Reference
In-Depth Information
be a therapeutic strategy in COPD and small molecule inhibitors are in
development.
The CCR3 are predominantly expressed on eosinophils and therefore
play an important role in asthma. In COPD, there is a small increase in
eosinophils and eosinophil basic proteins in induced sputum and bronchoal-
veolar lavage fluid and an increase in eosinophils has been described in
exacerbations of chronic bronchitis (68,103,104). This suggests that eosino-
phil chemoattractants may play some role. The RANTES (released by
activated normal T cells expressed and secreted, CCL5) activates CCR3
and is strongly expressed in airway epithelial cells of patients with chronic
bronchitis exacerbations (105). Eotaxin (CCL11) and CCR3 show increased
expression in the bronchi of patients with exacerbations of chronic bronchi-
tis and are correlated with increased numbers of eosinophils (106).
The CCR4 and CCR8 are selectively expressed on Th2 cells and are acti-
vated by the chemokines macrophage-derived chemokine (MDC, CCL22)
and thymus and activation-dependent chemokine (TARC, CCL17) (107).
However, Th2 cells are not prominent in COPD so it is unlikely that these
receptors are relevant.
The CCR7 plays a role in the migration of dendritic cells to regional
lymph nodes and therefore blocking this receptor might suppress antigen
presentation (108). There is an increase in the number of dendritic cells in
rat lungs exposed to cigarette smoke (109,110) and in the airways and alveo-
lar walls of smokers (111,112), but the chemotactic factors involved have
not yet been determined. The MIP-3
a
(CCL20) which acts on CCR6 that
is expressed by immature dendritic cells is potent chemoattractant of dendri-
tic cells and is expressed by airway epithelial cells in response to interferon-
g
(IFN-
g
) (113).
D. CX
3
C Chemokines
The unique CX
3
C chemokine fractalkine, which is tethered to cell surfaces,
shows increased expression in human airway epithelial cells after stimulation
with IFN-
g
and may be involved in recruitment and adhesion of monocytes,
T lymphocytes, and natural killer cells to epithelial surfaces (114). Whether
fractalkine or its receptor CX
3
CR1 is increased in COPD is not yet known.
VI. CYTOKINES
Since chronic inflammation is a prominent feature of COPD,
it is not
surprising that cytokines play a key role in its pathophysiology.
A. Tumor Necrosis Factor-
a
The TNF-
a
is present in high concentration in the sputum of COPD patients
(68), particularly during exacerbations (71). There is also an increase in
