title: ONO-5046 is a potent inhibitor of neutrophil elastase in human pleural effusion after lobectomy.
abstract: The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-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 alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sakuma
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Ohya
authors.forename: K
authors.initials: K
authors.lastname: Usuda
authors.forename: M
authors.initials: M
authors.lastname: Handa
authors.forename: T
authors.initials: T
authors.lastname: Abe
mesh_terms: D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D010996:Pleural Effusion / Q000201:enzymology*; D011013:Pneumonectomy; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D000515:alpha 1-Antitrypsin; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine