Table 3.
Antiproteases in the Respiratory Tract | Target Substrates | Sources in the Lung | Activity |
---|---|---|---|
TIMPs | MMPs (24) | Alveolar epithelial cells, alveolar macrophages, granulocytes (28, 97) | Insert reactive ridge NH2-terminal domain into MMP active site, inhibit apoptosis (103, 120) |
Serpin | Serine and cysteine proteases, caspases, bacteria, viruses (9, 57, 138, 141, 154) | Epithelial cells, alveolar macrophages (35, 115, 159) | Insert RCL into the active site of the targeted protease, inhibit LPS-induced inflammation, block microbial infection (101, 130) |
Trappin/Elafin | NE and proteinase-3, enveloped viruses (193) | Tracheal epithelial cells, club cells, type II cells, alveolar macrophages (123) | Contain WAP domain for antiprotease activity, inhibit viral infection (59, 150, 156, 187) |
SLPI | NE, cathepsin G, chymase, bacteria, and viruses (62, 184) | Epithelial cells, neutrophils, macrophages (48, 121) | Contain WAP domain for antiprotease activity, antimicrobial effects due to NH2-terminal domain and high cationicity, block inflammatory cascades, inhibit viral infection (67, 91, 93, 150, 156, 172, 173, 187) |
MMPs, matrix metalloproteinases; NE, neutrophil elastase; RCL, reactive center loops; SLPI, secretory leukocyte protease inhibitor; TIMPs, tissue inhibitors of metalloproteinases; WAP, whey acidic protein domain.