Biomedical Engineering Reference
In-Depth Information
and may thus impair the ability of macrophages to take up apoptotic neu-
trophils, resulting in increased numbers of apoptotic neutrophils in the air-
ways (90). Alveolar macrophages from COPD patients show defective
phagocytosis of apoptotic airway epithelial cells (91).
IX. CONCLUSIONS
Macrophages are multipotential inflammatory cells that play a key role in
the defense of the respiratory tract. Alveolar macrophages are activated
by irritants such as cigarette smoke, leading to a low-grade inflammatory
response through the release of neutrophil, monocyte, and T-lymphocyte
chemotactic factors. In COPD, this inflammatory response appears to be
greatly amplified, resulting in excessive inflammation leads to fibrosis of
small airways and release of excessive proteases resulting in destruction of
the lung parenchyma. The molecular basis for the amplification of the
inflammatory response of macrophages remains to be determined, but
may involve impairment of HDAC2 activity as a result of oxidative and
nitrative stress. It is likely that genetic factors are important in determining
this amplification, although the specific genes involved have not yet been
identified. The alveolar macrophages are resistant to inhibition by corticos-
teroids, reflecting the poor response to this treatment in COPD patients.
However, other treatments, such as theophylline, PDE inhibitors and in
the future resveratrol and IKK-2 inhibitors may be more effective. Target-
ing alveolar macrophages is a logical approach, since these cells appear to
play such a critical role in orchestrating the chronic inflammatory process
in COPD (92,93).
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