Animals, Binding Sites, Blotting, Western, Bronchoalveolar Lavage, Case-Control Studies, Catalytic Domain, Cathepsin B, Cathepsin L, Cathepsins, Chromatography, High Pressure Liquid, Cysteine Endopeptidases, Electrophoresis, Polyacrylamide Gel, Emphysema, Enzyme Activation, Enzyme Inhibitors, Epithelium, Female, Humans, Lung, Male, Middle Aged, Protein Binding, Proteinase Inhibitory Proteins, Secretory, Proteins, Recombinant Proteins, Secretory Leukocyte Peptidase Inhibitor, Threonine, Time Factors, Tyrosine, alpha 1-Antitrypsin
Health Research Board of Ireland, the Higher Education Authority of Ireland, the Charitable Infirmary Charitable Trust. Royal College of Surgeons in Ireland.
A number of serine proteases, matrix metalloproteases, and cysteine proteases were evaluated for their ability to cleave and inactivate the antiprotease, secretory leucoprotease inhibitor (SLPI). None of the serine proteases or the matrix metalloproteases examined cleaved the SLPI protein. However, incubation with cathepsins B, L, and S resulted in the cleavage and inactivation of SLPI. All three cathepsins initially cleaved SLPI between residues Thr(67) and Tyr(68). The proteolytic cleavage of SLPI by all three cathepsins resulted in the loss of the active site of SLPI and the inactivation of SLPI anti-neutrophil elastase capacity. Cleavage and inactivation were catalytic with respect to the cathepsins, so that the majority of a 400-fold excess of SLPI was inactivated within 15 min by cathepsins L and S. Analysis of epithelial lining fluid samples from individuals with emphysema indicated the presence of cleaved SLPI in these samples whereas only intact SLPI was observed in control epithelial lining fluid samples. Active cathepsin L was shown to be present in emphysema epithelial lining fluid and inhibition of this protease prevented the cleavage of recombinant SLPI added to emphysema epithelial lining fluid. Taken together with previous data that demonstrates that cathepsin L inactivates alpha(1)-antitrypsin, these findings indicate the involvement of cathepsins in the diminution of the lung antiprotease screen possibly leading to lung destruction in emphysema.
Medicine and Health Sciences
Taggart CC, Lowe GJ, Greene CM, Mulgrew AT, O'Neill SJ, Levine RL, McElvaney NG. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. Journal of Biological Chemistry. 2001;276(36):33345-52
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.