Fibronectin degradation in chronic wounds depends on the relative levels of elastase, α1-proteinase inhibitor, and α2-macroglobulin

The goal of our studies was to learn about the mechanism of fibronectin degradation in chronic ulcers, We found that the appearance of fibronectin fragments in chronic ulcer wound fluid correlated with elevated levels of elastase and cleavage of the proteinase inhibitors α2-macroglobulin (α2-M) and α1-proteinase inhibitor (α1-PI). Some wound fluid samples retained the capacity to degrade fibronectin in vitro. Degradation of fibronectin by these samples was blocked by specific inhibitors of neutrophil elastase but not by inhibitors of metalloproteinases. Addition of human neutrophil elastase to mastectomy fluid, an acute wound fluid, resulted in formation of α1-PI and α2-M complexes and cleavage products resembling those observed in chronic wound fluid. Moreover, degradation of fibronectin and processing of matrix metalloproteinase MMP-9 occurred under these conditions. Taken together, our findings suggest that elevated levels of neutrophil elastase are responsible for fibronectin degradation in the chronic wound environment.