Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha(1)-protease inhibitor caused by different forms of oxidative stress

Secretory leukoprotease inhibitor (SLPI) and alpha(1)-protease inhibitor (alpha(1)-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha(1)-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha(1)-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated, The resulting anti-NE activity of rSLPI was not significantly different from that of alpha(1)-PI after exposure to NCS (p>0.5), chloramines (p>0.6), activated PMNs (p> 0.07) and activated AMs (p>0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha(1)-protease inhibitor lose antineutrophil elastase activity to a similar extent when expressed to conditions that may be present in inflammatory lung disorders.