Biomedical Engineering Reference
In-Depth Information
the inhibitory effect of SLPI is unaffected (157). It has also been suggested
that adhesion to goblet cells may alter the neutrophil membrane, enhancing
the release of membrane bound NE into the intercellular space (158), and
this process may result in mucus secretion.
Neutrophil elastase may play a role in recruiting more neutrophils in
response to inflammation, further enhancing the inflammatory burden.
The proteinase stimulates the release of LTB4 by macrophages (159) and
may cause release of CXCL8 from bronchial epithelial cells that would
amplify the chemoattractant gradient and hence cellular response. This
amplification is greater in patients deficient in
a
1
-AT as reflected by their
higher levels of LTB4 and elastase and thus provides a greater potential
for tissue destruction than patients with normal antiproteinase function
thereby explaining their more severe and rapidly progressive disease (42).
As well as causing damage leading to emphysema, NE has been shown
to cause mucus hypersecretion which is a feature of COPD. Animal models
have demonstrated that NE can induce secretory cell metaplasia, which is
prevented by NE specific inhibitors (158,160,161). The mechanism for these
changes has not been totally clarified, but may involve the mucous gland
epidermal growth factor receptor interacting with NE as part of a signaling
cascade (162). In human studies, however, there is a clear relationship
between the amount of mucus production and the concentration of active
NE in the secretions (Fig. 5).
Neutrophil elastase can damage the respiratory epithelium in vitro
(163), reduce ciliary beating (164), and trigger a state of oxidative stress in
Figure 5
The relationship between sputum volume and NE activity. The active
concentration of NE using a synthetic substrate, maapvpna, is shown on the horizon-
tal axis for individual sputum samples from patients with bronchiectasis. The results
are plotted against the sputum volume produced (vertical axis). The correlation
coefficient of the relationship is shown (p
<
0.002). (From Ref. 17.)
