Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-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 alpha2-macroglobulin (alpha2-M) and alpha 1-proteinase inhibitor (alpha1-P1). 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 alpha1-PI and alpha2-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.
Grinnell
F
F
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical School, Dallas, TX 75235, USA.
Zhu
M
M
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000032:analysis; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008408:Mastectomy; D020780:Matrix Metalloproteinase 9; D010196:Pancreatic Elastase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis; D010641:Phenotype; D011480:Protease Inhibitors / Q000032:analysis*; D014456:Ulcer / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000032:analysis*
D005353:Fibronectins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; D003094:Collagen; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D017364:Collagenases; D020780:Matrix Metalloproteinase 9