Biomedical Engineering Reference
In-Depth Information
metalloproteinase is able to cleave transmembrane amphiregulin, a ligand
for the EGFR. The binding of amphiregulin to EGFR then triggers recep-
tor's activation (76). Of interest, cigarette smoke can also cause neutrophil
migration into the airways (77). Neutrophils are also increased in the bron-
chial glands (78). In vivo and in vitro studies show that these neutrophils can
stimulate goblet cell degranulation (79). Purified neutrophil elastase has
been shown to be a potent secretagogue for goblet cells in vitro (80). How-
ever, it is not clear whether this molecule is responsible for the effect of neu-
trophils on degranulation, since the cells themselves release little or no
elastase in vitro, even after activation with a variety of molecules (IL-8,
LTB4, TNF-
a
). Rather, the activation of neutrophils causes a translocation
of elastase from the azurophilic granules to the cell surface (81). However, in
a guinea pig model, the elastase inhibitor ICI 200355 inhibited the neutro-
phil-dependent goblet cell degranulation seen after the trachea instillation
of neutrophil chemoattractants (82). These results confirmed the role of neu-
trophil elastase in degranulation, but the question of how elastase exerts its
effect still remains since neutrophil activators and chemoattractants do not
appear to promote its release (83). The potential role of elastase in goblet
cell degranulation implies a direct interaction between neutrophils and gob-
let cells. Some experimental evidence suggests a direct interaction between
neutrophils and goblet cells in the airway epithelium, involving ICAM-1,
CD11b, or CD 18 cells (83). These leukocyte adhesion receptors play an
important role in inflammation via their regulatory effects on leukocyte
adhesion, transmigration, and function (84).
B. Asthma
Like in COPD, airway wall inflammation is thought to play a central role
also in the development and progression of asthma. The currently available
knowledge on associations between inflammation and airway function,
including airflow obstruction and bronchial hyperresponsiveness, is based
on both acute inflammatory events, such as airway smooth-muscle contrac-
tion and
=
or (sub) mucosal swelling, secondary to activation of inflammatory
and resident cells within the airway wall, as well as chronic airway inflam-
mation, associated with subepithelial collagen deposition, smooth-muscle
growth, and increased mucosal vascularity (85,19). The pattern of inflamma-
tion varies considerably from COPD patients and depends on the stage of
the disease. The degree of airway inflammation varies with the severity
and chronicity of the disease and may also determine the responsiveness
of the patient to treatment (86).
Infiltration of the airway by lymphocytes and eosinophils have been
found in patients with mild-to-moderate chronic asthma. However, inflam-
mation in chronic asthma appears to be far more complex than a simple
eosinophilic inflammation alone. All cells of the airways, including T cells,
