Biomedical Engineering Reference
In-Depth Information
Table 1
The Important Effects of NE in COPD
Cellular interactions
Neutrophils and
macrophages
NE
=
a
1
-AT complexes are chemotactic for neutrophils (193)
NE
=
a
1
-AT complexes increase
a
1
-AT secretion by monocytes
and alveolar macrophages (194)
NE increases LTB4 secretion by macrophages (159)
Increases
a
1
-AT expression by monocytes and alveolar
macrophages (194)
Epithelial cells
Disruption and detachment (167)
Reduces ciliary beating (163)
Enhances oxidative stress (165)
Induces apoptosis (166)
Enhances production of CXCL8 (195)
Increase SLPI expression but reduces secretion of SLPI (196)
Increase elafin expression (197)
Increase mucin MUC5AC protein content (198)
Increases bacterial adherence and colonization (199)
Endothelial cells
Induces detachment and apoptosis (168)
Bacteria
NE mediates bacterial killing (207)
Degradation
Degrades elastin, fibronectin, and other matrix compounds (17)
Degrades T lymphocyte surface antigen (200)
Degrades Cystatin C (201)
Degrades TIMPs (188)
Activation
Activates secreted MMP-2, MMP-2, MMP-3, and MMP-9
(189,202)
Activates Cathepsin B (201)
antiproteinases such as
a
1
-antitrypsin (
a
1
-AT) and secretory leucocyte pro-
teinase inhibitor (SLPI), thereby limiting tissue damage (see Table 2 for anti-
proteinases important in COPD). In COPD, an imbalance exists, either
from the increased activity of proteinases or from a deficiency in antiprotei-
nases, which leads to tissue destruction. The theory originated from the
observation that patients with
a
1
-AT deficiency (
a
1
-ATD) were predisposed
towards the early onset of emphysema (13) and that enzymes normally
inhibited by
a
1
-AT can cause experimental emphysema (see the later sec-
tion).
This chapter will summarize neutrophil maturation and structure,
along with the pulmonary chemoattractants. Neutrophil migration into lung
will be outlined, with particular reference to COPD, and the evidence for the
actions of neutrophil proteinases in the pathogenesis of COPD will be
reviewed, highlighting in vitro and in vivo work.
