ONO-5046 is a potent inhibitor of neutrophil elastase in human pleural effusion after lobectomy

Abstract

The imbalance of neutrophil elastase and α 1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzoyl]aminoacetic acid (ONO-5046) and purified α 1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to α 1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The α 1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala) 3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not α 1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and α 1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.