The role of thiol proteases in tissue injury and remodeling
| Autor: | J. S. Munger, Harold A. Chapman, Guo-Ping Shi |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cathepsin Cathepsin H biology Sequence Homology Amino Acid Molecular Sequence Data Cathepsin E Critical Care and Intensive Care Medicine Cathepsin A Cathepsins Cathepsin B Cathepsin C Cathepsin L Cysteine Endopeptidases Biochemistry Macrophages Alveolar biology.protein Animals Humans Amino Acid Sequence Lysosomes Lung Cathepsin S |
| Zdroj: | American journal of respiratory and critical care medicine. 150(6 Pt 2) |
| ISSN: | 1073-449X |
| Popis: | Human lung macrophages express all four of the known lysosomal thiol proteases: cathepsins B, H, L, and S. These enzymes share a similar size and targeting mechanism for lysosomal accumulation and all have relatively indiscriminate substrate specificity in comparison with such highly selective serine proteases as urokinase or thrombin. These enzymes do have distinctive properties: only cathepsin B has C-terminal dipeptidase activity, only cathepsin H has potent aminopeptidase activity, and only cathepsin L and S are elastolytic. Cathepsin S is unique in that it is stable at neutral pH; indeed, at neutral pH it has elastolytic activity roughly comparable with that of neutrophil elastase. Recent studies of the differential expression of these cathepsins suggest they not only cooperate in terminal degradation of endocytized protein but also have specific functions such as proenzyme activation, antigen processing, and tissue remodeling, especially bone matrix resorption. Lysates of lung macrophages degrade elastin at neutral pH, suggesting that necrosis of macrophages at sites of macrophage accumulation, e.g., caseation necrosis, could contribute to tissue destruction. Tissue destruction and remodeling by thiol proteases expressed by live macrophages, however, is limited by tight compartmentalization of cathepsins to lysosomes. Nonetheless, macrophages accumulate at sites of known injury in cigarette smokers. Because these cells contain potent elastases, and because lysosomal enzyme release and cell surface acidification are regulated events, dysregulation of thiol protease expression in stimulated macrophages may contribute to the injury observed in cigarette smokers with non-alpha-1-protease inhibitor-type emphysema. |
| Databáze: | OpenAIRE |
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