FIBRONECTIN DEGRADATION IN CHRONIC WOUNDS DEPENDS ON THE RELATIVE LEVELS OF ELASTASE, ALPHA-1-PROTEINASE INHIBITOR, AND ALPHA-2-MACROGLOBULIN

The goal of our studies was to learn about the mechanism of fibronecti n degradation in chronic ulcers, We found that the appearance of fibro nectin fragments in chronic ulcer wound fluid correlated with elevated levels of elastase and cleavage of the proteinase inhibitors alpha 2- macroglobulin (alpha 2-M) and alpha 1-proteinase inhibitor (alpha 1-PI ). Some wound fluid samples retained the capacity to degrade fibronect in in vitro. Degradation of fibronectin by these samples was blocked b y specific inhibitors of neutrophil elastase but not by inhibitors of metalloproteinases. Addition of human neutrophil elastase to mastectom y fluid, an acute wound fluid, resulted in formation of alpha 1-PI and alpha 2-M complexes and cleavage products resembling those observed i n chronic wound fluid. Moreover, degradation of fibronectin and proces sing of matrix metalloproteinase MMP-9 occurred under these conditions . Taken together, our findings suggest that elevated levels of neutrop hil elastase are responsible for fibronectin degradation in the chroni c wound environment.