Secretory leukocyte proteinase inhibitor and elafin are resistant to degradation by MMP-8

The naturally occurring neutrophil elastase inhibitors, alpha(1)-proteinase inhibitor (alpha(1)PI), secretory leukocyte proteinase inhibitor (SLPI), and elafin, are potential therapeutic agents in the treatment Of neutrophil-mediated lung disease. However, a IN has been shown to be susceptible to inactivation by matrix metalloproteinases (MMPs) released by neutrophils, particularly neutrophil collagenase (MMP-8). The aim of this study was to determine if SLPI and elafin are similarly susceptible to degradation by this neutrophil-specific MMP The effect of MMP-8 on SLPT and elafin was assessed by determining the neutrophil elastase inhibitory capacity (NEIC) and electrophoretic protein profile of both inhibitors following exposure to purified MMP-8. As a positive control, the effect of MMP-8 alpha(1)PI was assessed in parallel Although treatment of alpha(1)PI with MMP-8 resulted in a significant decrease in its NEIC (P = .025), no similar decrease was observed with SLPI or elatin. Electrophoretic analysis confirmed digestion of alpha(1)PI by MMP-8 but no digestion of either SLPI or elafin was observed. These results demonstrate that SLPI and elafin are resistant to proteolytic inactivation by MMP-8, a property that may enhance their therapeutic application in neutrophil-mediated inflammatory lung disease.