PT  - JOURNAL ARTICLE
AU  - J. Cooley
AU  - M.K. Sontag
AU  - F.J. Accurso
AU  - E. Remold-O'Donnell
TI  - SerpinB1 in CF airway fluids: quantity, molecular form and mechanism of elastase inhibition
AID  - 10.1183/09031936.00073710
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00737-2010
4099  - http://erj.ersjournals.com/content/early/2010/08/20/09031936.00073710.short
4100  - http://erj.ersjournals.com/content/early/2010/08/20/09031936.00073710.full
AB  - Neutrophil serine proteases (NSPs) especially elastase are major agents of lung destruction in cystic fibrosis (CF) patients. This study investigated SerpinB1, a highly efficient inhibitor of NSPs, in CF lung diseaseBronchoalveolar lavage fluid (BALF) from 31 children with CF and 24 control children were examined for amount and molecular species of SerpinB1, and its mechanism of action was studied.CF BALF had more SerpinB1 than control BALF, 3.9 (2.60 – 5.62) μg/ml (geometric means, 95% confidence intervals) versus 1.37 (1.20–1.55) μg/ml, p<0.001). BALF levels of SerpinB1 were higher for infected versus non-infected CF subjects (5.5 versus 2.7 μg/ml, p<0.04) and substantially higher for elastase-positive versus elastase-negative CF subjects (8.41 versus 1.89 μg/ml, p<0.001). Most SerpinB1 in CF BALF had been cleaved. Adding recombinant SerpinB1 to CF BALF stoichiometrically inhibited endogenous elastase, indicating that the inhibitor functions in the CF microenvironment. In vitro simulations comparing SerpinB1 and α1antitrypsin (SerpinA1) showed that both rapidly form irreversible inhibitory covalent complexes with elastase and that these differed in survival time. The SerpinB1-elastase complex survived only briefly due to fragmentation of bound elastase, releasing cleaved SerpinB1, the molecular form in CF BALF.The findings define an innate role for SerpinB1 in CF airways.