title: Human cysteine cathepsins are not reliable markers of infection by Pseudomonas aeruginosa in cystic fibrosis.
abstract: Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+) and P. aeruginosa-negative (6 Ps-) samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (∼2-fold) in the Ps+ and Ps- groups (p<0.001), which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens). Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps- samples, despite the possible release of the ∼31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection.
authors: Inserm U618, Université François Rabelais, Protéases et Vectorisation Pulmonaires, Tours, France.
authors: Clément
authors: C
authors: Naudin
authors: Alix
authors: A
authors: Joulin-Giet
authors: Gérard
authors: G
authors: Couetdic
authors: Patrick
authors: P
authors: Plésiat
authors: Aneta
authors: A
authors: Szymanska
authors: Emilia
authors: E
authors: Gorna
authors: Francis
authors: F
authors: Gauthier
authors: Franciszek
authors: F
authors: Kasprzykowski
authors: Fabien
authors: F
authors: Lecaille
authors: Gilles
authors: G
authors: Lalmanach
mesh_terms: D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002403:Cathepsins / Q000737:chemistry / Q000378:metabolism*; D015891:Cystatins / Q000378:metabolism; D003545:Cysteine; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism; D011552:Pseudomonas Infections / Q000201:enzymology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D013183:Sputum / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D007704:Kininogens; D002403:Cathepsins; D003545:Cysteine