Association of Airway Cathepsin B and S With Inflammation in Cystic Fibrosis

作者：Martin S L^*; Moffitt K L; McDowell A; Greenan C; Bright Thomas R J; Jones A M; Webb A K; Elborn J S

来源：Pediatric Pulmonology, 2010, 45(9): 860-868.

DOI：10.1002/ppul.21274

• cathepsin
• cysteine proteinase
• cystic fibrosis
• inflammation
• neutrophil elastase

Irreversible tissue damage within the cystic fibrosis (CF) lung is mediated by proteolytic enzymes during an inflammatory response. Serine proteinases, in particular neutrophil elastase (NE), have been implicated, however, members of the cysteine proteinase family may also be involved. The aim of this study was to determine cathepsin B and S levels in cystic fibrosis (CF) sputum and to assess any relationship to recognized markers of inflammation such as sputum NE, interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), urine TNF receptor 1 (TNFr1), plasma IL-6, and serum C-reactive protein (CRP). Proteinase activities were measured in the sputum of 36 clinically stable CF patients using spectrophotometric and fluorogenic assays. Immunoblots were also used to confirm enzyme activity data. All other parameters were measured by ELISA. Patients had a mean age of 27.2 (8.2) years, FEV. of 1.6 (0.79) L and BMI of 20.7 (2.8). Both cathepsin B and S activities were detected in all samples, with mean concentrations of 18.0 (13.5) mu g/ml and 1.6 (0.88) mu g/ml, respectively, and were found to correlate not only with each other but with NE, TNF-alpha and IL-8 (in all cases. <0.05). Airway cathepsin B further correlated with circulatory IL-6 and CRP, however, no relationship for either cathepsin was observed with urine TNFr1. This data indicates that cathepsin B and S may have important roles in the pathophysiology of CF lung disease and could have potential as markers of inflammation in future studies. Pediatr Pulmonol. 2010; 45:860-868.

• 出版日期2010-9