MR889 is a synthetic inhibotor of human neutrophil elastase with potential in clinical conditions characterized by a high load of this proteolytic enzyme, mainly chronic obstructive pulmonary disease. On the basis of its mechanism of inhibition, it has been suggested that MR889, upon reaction with elastase, would generate new free thiol groups. The aim of this study was to investigate whether MR889, upon reaction with elastase, may modify rheologic properties, i.e. apparent viscosity and elasticity, of both human sputum and porcine stomach mucus, in ex-vivo and in vitro experiments. MR889 10-4 M alone had no effect rheologic properties of samples, whereas an agent with free thiol group, n-acetylcysteine 10-4 M reduced both viscosity and elasticity. MR889 10-4 M upon reaction with elastase 0.03 nMol (giving 83% of elastase inhibition) had no effect on rheologic properties of samples, whereas upon reaction with elastase 0.15 nMol (49% inhibition) yielded a marked decrease in viscosity. This result would suggest that MR889, in the presence of a high load of elastase, may acquire direct mucus modifying capacity, likely because of its greater utilization upon reaction with the enzyme.
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