We have studied the effects of the mucolytic thiol agent mercapto-ethanesulphonate (mesna) on the activity of both polymorphonuclear leucocyte (PMN) elastase and antileucoprotease in vitro. In all tests a specific synthetic substrate was used to measure elastase activity, which was then related to enzyme activity in the absence of mesna. The relative elastase activity decreased to 67.5% of control values after the enzyme had been incubated in a 120 mmol/l mesna solution. In the sol phase of purulent sputum, elastase activity decreased to 45% after the sol phase had been incubated in a 600 mmol/l mesna solution. The inability to reverse the inhibition of mesna by increasing the substrate concentration indicated that mesna acts as a non-competitive inhibitor of PMN elastase. Incubation of elastase with antileucoprotease reduced the relative elastase activity to 21%. When antileucoprotease was preincubated in a 60 mmol/l mesna solution under identical assay conditions, a relative elastase activity of 39% was observed. Inhibition experiments with mesna treated antileucoprotease, in which sulphydryl groups were blocked with iodoacetamide, strongly suggested that the dissociation constant (Ki) of the fraction of antileucoprotease that retains activity after the incubation with mesna was not changed. Elastase inhibitory activity in mucoid sol phase, which can be ascribed mainly to antileucoprotease, decreased to 53% after incubation with mesna at a concentration of 960 mmol/l. Incubation of PMN elastase/antileucoprotease complex with mesna did not result in any release of active PMN elastase from the antileucoprotease. It is concluded that mesna and other thiol compounds, when locally administered, may influence the proteinase-antiproteinase balance in the airways by their effect on both PMN elastase and antileucoprotease.
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