Cysteine cathepsins in human silicotic bronchoalveolar lavage fluids.
Mature, active cysteine cathepsins (CPs) were identified in human inflammatory bronchoalveolar lavage fluid (BALF) supernatants from patients suffering from silicosis by both western blot and surface plasmon resonance analyses. BALFs are not a reservoir of activatable proforms, since no autocatalytic maturation at acidic pH occurs. Cathepsin H is the most profuse among studied CPs (median value: 36.5 nM), while cathepsins B and L are the two most abundant thiol-dependent endoproteases. The overall concentration of active cathepsins B, H, K, L, and S is approximately 10-fold lower than their concentration in BALF supernatants from patients suffering from inflammatory acute lung injuries (962+/-347 nM).The cathepsins (approximately 70 nM)/cystatin-like inhibitors (approximately 9 nM) ratio is unbalanced in favor of enzymes ( approximately 8-fold). This presence of uncontrolled CPs suggests that they may contribute, in addition to matrix metalloproteases, to the lung tissue breakdown/remodeling occurring during silicosis, although their exact contribution to interstitial inflammation remains to be evaluated.
Perdereau
Céline
C
INSERM U618, Protéases et Vectorisation Pulmonaires, Equipe Protéases et Pathologies Pulmonaires, Université François Rabelais, Faculté de Médecine, 10 Boulevard Tonnellé, F-37032 Tours Cedex, France.
Godat
Emmanuel
E
Maurel
Marie-Christine
MC
Hazouard
Eric
E
Diot
Elisabeth
E
Lalmanach
Gilles
G
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002403:Cathepsins / Q000737:chemistry / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012829:Silicosis / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D020033:Protein Isoforms; D002403:Cathepsins; D003545:Cysteine