Biomedical Engineering Reference
In-Depth Information
response to lipopolysaccharide (LPS) compared to that of non-smokers.
This may be due to the elevated release of inflammatory mediators that
may activate NF-
k
B. However, activation of the MAP kinase pathways
[ERK, stress activated protein kinase (SAPK), and p38] was differentially
regulated. Activation of p38 was more rapid in BAL cells from smokers
compared to the activity of ERK and SAPK. They also suggested that
the differences in activation of NF-
k
B and MAP kinases in BAL cells from
smokers and non-smokers may be related to the differences in their micro-
environment, which is affected by chronic exposure to cigarette smoke. The
activation of p38, therefore, may be responsible for the elevated levels of
TNF-
a
and IL-8 seen in BALF and sputum of patients with COPD (86).
B. Pro-Inflammatory Genes
Evidence from a large number of studies indicates that COPD is associated
with airway and airspace inflammation and by the presence of markers of
inflammation, including IL-8 and TNF
a
which are elevated in the sputum
of patients with COPD (86). Studies in vitro show that treatment of macro-
phages, alveolar and bronchial epithelial cells with oxidants stimulate the
release of inflammatory mediators such as IL-8, IL-1, and nitric oxide. This
is associated with increased expression of the mRNA for the genes for these
inflammatory mediators, and increased nuclear binding and activation of
NF-
k
B (87,88). Similarly, several investigators have shown that cigarette
smoke induces IL-8 release from human bronchial and endothelial cells
which may contribute to airway inflammation in smokers (85,89). The
increased IL-8 was significantly correlated with neutrophil counts in bron-
chial samples of BALF (85).
Cigarette smoke has been shown in vivo to be a cause of increased
adherence of leukocytes to vascular endothelium (23). Shen et al. (90) have
shown that cigarette smoke condensate induces the expression of a subset of
cell adhesion molecules, such as intercellular adhesion molecule (ICAM-1),
endothelial leukocyte adhesion molecule 1 (ELAM-1), and vascular cell
adhesion molecule (VCAM-1) in human umbilical vascular endothelial cells
associated with an increase in the binding activity of NF-
k
B suggesting the
increased transendothelial migration of monocytes by cigarette smoking.
The release of pro-inflammatory mediators, such as IL-l
b
and sICAM-1,
was increased by cigarette smoke exposure in bronchial epithelial cells cul-
tured from biopsy materials obtained from patients with COPD compared
to smokers (91). Similarly, primary cultured human bronchial epithelial cells
obtained from patients with COPD showed higher levels of TNF-
a
-induced
release of IL-6 and IL-8 compared to non-stimulated COPD cells (92).
Surprisingly, the response was not different in cells obtained from current
=
ex-smokers. These studies suggest that patients with COPD have a greater
susceptibility to the effects of cigarette smoke.
