166 The Role of Serine Proteases and their Inhibitors in Chronic Wounds

Abstract

The role of proteases in chronic wounds has been the subject of many investigations in recent years. These studies have reported biochemical differences between chronic and acute wound fluids and have shown that elevated levels of proteases, in particular the matrix metalloproteinases are abundant in chronic wounds. While this has led to the hypothesis that the chronic wound environment is hostile and not conducive to wound repair, it is still unknown whether this is due to a direct or indirect defect in protease regulation or their inhibitors. We hypothesize that an excess of proteases, specifically the serine proteases present in chronic wounds, are primarily responsible for this hostile wound environment. These proteases degrade endogenous growth factors, reducing their efficacy and delaying healing. In this study, fluid and tissue from chronic and acute wounds were collected over a 24-hour period. Using ELISA, samples were assessed for protease activity (specifically elastase and typsin-like enzymes), their inhibitors and growth factors. Our results show that serine proteases, predominantly elastase, were significantly elevated in the chronic wound fluids. The serpins designed to control these proteases were not up-regulated when compared to the acute controls, resulting in excessive proteolytic activity. An increase in serine protease production without an increase in their serpins is thought to result in a reduction in growth factors, an effect, which was also observed in the chronic wound samples. This work indicates that there is an imbalance in the ratio of inhibitor to enzyme, due to an up regulation of protease production in chronic wounds. We also conclude that misregulation of serine proteases may be responsible for the observed excessive degradation of the extracellular matrix and growth factors in these chronic wounds.