Biomedical Engineering Reference
In-Depth Information
13
Antiproteases
Noel G. McElvaney and Clifford Taggart
Pulmonary Research Division, Department of Medicine, Royal College of
Surgeons in Ireland, Education and Research Centre, Beaumont Hospital,
Dublin, Ireland
I.
INTRODUCTION
The function of antiproteases is to inhibit the activity of cognate proteases
thereby preventing potentially damaging degradation of host tissue. In the
context of the respiratory tract, the primary antiproteases of interest are
alpha-1-antitrypsin (AAT), secretory leukoprotease inhibitor (SLPI),
elafin, tissue inhibitors of metalloproteases (TIMPs), and cystatins. The pri-
mary protease targets of AAT, SLPI, and elafin are the serine proteases,
neutrophil elastase (NE), proteinase 3, and cathepsin G, which are released
by activated neutrophils. Tissue inhibitors of metalloproteases inhibit the
activity of matrix metalloproteases (MMPs) that are released from activated
neutrophils and macrophages, whereas cystatins inhibit the activity of elas-
tolytic cathepsins that are released from macrophages, fibroblasts, and
epithelial cells. Despite the emphasis on protease inhibitory function, it
has become apparent in recent years that antiproteases possess other bio-
logical functions including antibacterial, anti-inflammatory, and immuno-
modulatory properties. In the course of this chapter, we will outline the
biological function of each of the antiproteases mentioned earlier and
discuss how antiprotease activity may be compromised in the setting of
lung disease.
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