Biomedical Engineering Reference
In-Depth Information
B. Theophylline
Theophylline in low concentrations increases HDAC activity in alveolar
macrophages and in vitro reverses the steroid resistance induced by
oxidative stress (80). This may account for the anti-inflammatory effect of
low-dose theophylline seen in COPD, in marked contrast to the resistance
to corticosteroids (81). This suggests that theophylline has the potential to
even unlock the resistance to corticosteroids in the treatment of COPD
(82). In higher concentrations, theophylline has an inhibitory effect on
alveolar macrophages through phosphodiesterase (PDE) inhibition (83).
C. Phosphodiesterase Inhibitors
Several PDEs are expressed in alveolar macrophages, suggesting that PDE
inhibitors may have inhibitory effects on macrophage function. Alveolar
macrophages express PDE 3, 4, and 7A (84). Studies with inhibitors demon-
strate that both PDE3 and PDE4 inhibitors suppress macrophage activity,
but PDE4 inhibitors are less effective than in monocytes (83). A clinical trial
of a PDE4 inhibitor cilomilast has shown a reduction in the numbers of
macrophages (CD68
รพ
cells) in the airways of COPD patients, presumably
through inhibition of monocyte recruitment into the lungs (85).
D. Resveratrol
Resveratrol, a flavenoid found in red wine, is an effective inhibitor of cyto-
kine expression from macrophages from COPD patients, but its molecular
mechanisms of action have not yet been determined (86). Resveratrol
appears to inhibit NF-
k
B and AP-1, suggesting that it inhibits the activation
of these transcription factors and thus the expression of multiple inflamma-
tory genes, possibly through the activation of an unknown nuclear receptor.
VIII. PHAGOCYTIC FUNCTION
Macrophages are phagocytic for particles and bacteria and play an impor-
tant role in host defense. The receptors on macrophages that mediate pha-
gocytosis are largely unknown (87). The macrophage scavenger receptor
MARCO appears to play an important role in phagocytosis of bacteria,
but its role in COPD has not yet been explored. The phagocytic potential
of macrophages from COPD patients has not been explored, but it is possi-
ble that impaired phagocytosis may result in the increased bacterial load in
the respiratory tract of patients with COPD.
Macrophages recognize apoptotic cells via expression of phosphatidyl-
serine (PS) which interacts with specific receptors on the macrophage
surface (88). Ingestion of apoptotic granulocytes by macrophages induces
the secretion of TGF-
b
1 (89). Neutrophil elastase cleaves the PS receptor
