SECRETORY LEUKOCYTE PROTEINASE INHIBITOR AND ELAFIN ARE RESISTANT TO DEGRADATION BY MMP-8

Abstract

The naturally occurring neutrophil elastase inhibitors, α 1 -proteinase inhibitor (α 1 PI), secretory leukocyte proteinase inhibitor (SLPI), and elafin, are potential therapeutic agents in the treatment of neutrophil-mediated lung disease. However, α 1 PI has been shown to be susceptible to in activation 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 SLPI 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 α 1 PI was assessed in parallel. Although treatment of α 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 α 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.

• Alpha1-PROTEINASE Inhibitor
• Elafin
• Elastase Inhibitors
• Matrix Metalloprotein 8
• Oxidation
• Secretory Leukocyte Protein Inhibitor