Active cathepsins B, H, K, L and S in human inflammatory bronchoalveolar lavage fluids.
BACKGROUND
Chronic inflammation and tissue remodelling result from an imbalance between proteolytic enzymes and their inhibitors in the lungs in favour of proteolysis. While many studies have examined serine proteases (e.g. cathepsin G and neutrophil elastase) and matrix metalloproteases, little is known about the role of papain-like CPs (cysteine proteases). The present study focuses on the thiol-dependent cathepsins (CPs) and their specific cystatin-like inhibitors [CPIs (CP inhibitors)] in human inflammatory BALFs (BAL fluids, where BAL stands for broncho-alveolar lavage).


RESULTS
Cathepsins B, K and S found were mostly zymogens, whereas cathepsins H and L were predominantly in their mature forms. Little immunoreactive cystatin C was found and the high- and low-molecular-mass ('weight') kininogens were extensively degraded. The BALF procathepsins B and L could be activated autocatalytically, indicating that alveolar fluid pro-CPs are reservoirs of mature enzymes. Hydrolysis patterns of 7-amino-4-methylcoumarin-derived peptide substrates showed that extracellular alveolar CPs remain proteolytically active, and that cathepsins B and L are the most abundant thiol-dependent endoproteases. The CP/CPI balance was significantly tipped in favour of cathepsins (3- or 5-fold), as confirmed by the extensive CP-dependent degradation of exogenous kininogens by BALFs.


CONCLUSIONS
Although their importance for inflammation remains to be clarified, the presence of active cathepsins L, K and S suggests that they contribute to the extracellular breakdown of the extracellular matrix.
Serveau-Avesque
Carole
C
INSERM U618, Tours, France.
Martino
Michèle Ferrer-Di
MF
Hervé-Grépinet
Virginie
V
Hazouard
Eric
E
Gauthier
Francis
F
Diot
Elisabeth
E
Lalmanach
Gilles
G
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002384:Catalysis; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007704:Kininogens / Q000378:metabolism; D011014:Pneumonia / Q000201:enzymology* / Q000276:immunology; D011498:Protein Precursors / Q000378:metabolism
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D004791:Enzyme Inhibitors; D007704:Kininogens; D011498:Protein Precursors; D002403:Cathepsins