Biomedical Engineering Reference
In-Depth Information
sema (37). NE were protected by 2
=
3 from the development of emphysema
in response to cigarette smoke (38). This was both a direct effect of NE as
well as from its ability to inactivate tissue inhibitors of metalloproteinases
(TIMPs) and mediate monocyte migration into the lung. In turn, MMP-
12 degrades
a
1-AT, and MMP-12 may influence neutrophil recruitment
via TNF-shedding (39). Thus, NE and MMP-12 interact to enhance the
activity of the other in COPD.
IV.
SUMMARY
In summary, proteinases have been strongly implicated in the pathogenesis
of COPD for decades. Recently, we have realized that there are multiple
proteinases involved including serine, cysteine, and matrix metallo-
proteinases. Moreover, they are expressed by a variety of inflammatory
and immune cells, as well as structural cells of the lung. In addition to their
matrix destructive role, we now appreciate additional functions such as their
participation in inflammatory cell movement by generating and removing
chemotactic gradients. Future studies should focus on the relationship
between inflammation-structural cell apoptosis and the role of proteinases
in these processes. Finally, we have yet to apply proteinase inhibitors long
term for COPD. Determining the safety and efficacy of inhibition should
be a priority.
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