Effect of metabolite I of erdosteine on the release of human neutrophil elastase

Erdosteine is a mucolytic drug whose metabolization gives rise to an active metabolite with an SH group (Met 1), which reduces neutrophil release of reactive oxygen species and the peroxynitrite generated by the reaction of superoxide anion with nitric oxide, thus disrupting the phlogogenic loop sustained by activated neutrophils. Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin and is considered to be pivotal in the pathogenesis of respiratory tract inflammation. The aim of this study was to examine whether, in addition to reducing the generation of free radicals, Met I can also interfere with the human neutrophil release of elastase. After the neutrophils were incubated with increasing amounts of Met 1 (1.25, 2.5, 5, 10, 20 mu g/ml), elastase exocytosis was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that Met I significantly inhibits fMLP-induced elastase release by neutrophils in a concentration-dependent manner from 2.5 to 20 mu g/ml. Our findings may be clinically relevant because the inhibitory effects were obtained at Met I concentrations that are achievable in the clinical setting. By reducing elastase and oxidant radical release (two major components of the inflammatory process), Met I have clinically useful anti-inflammatory effects. Copyright (c) 2006 S. Karger AG, Basel.