172 Neutrophil Enzymes in Pressure Ulcers

Abstract

It has been speculated that a prolonged and elevated neutrophilic response has an important role in the pathogenesis of chronic wounds. This has raised the possibility that one or more of these proteases might be useful as a diagnostic or prognostic biomarker for chronic wounds. The purpose of this study was to examine several primarily neutrophil-derived proteases present in pressure ulcer tissues and to determine whether protease activity could be correlated with neutrophil levels. Biopsies of pressure ulcers were taken from consented subjects (n = 13) and again after 3 months standard care. Mean wound volume decreased 2.4 cm3 per month; however, volumes of six wounds were increased at the end of the study. Levels of extractable myeloperoxidase (MPO), elastase, collagenase-2 (MMP-8), and gelatinase (MMP-9) activities were determined. Mean levels of MPO (n = 11) at study initiation and after 3 months were nearly identical (2945 and 2845 milliunits per mg extract, respectively). Interestingly, these levels were similar to that previously found in healing open dermal wounds at 4 days postwounding. MPO levels increased in the extracts obtained from three subjects and declined in five subjects. Elastase (corr. 0.265 p = 0.233) and MMP-8 (corr. −0.05 p = 0.835) activities correlated poorly with MPO. This is likely a reflection of differences in the access of protease inhibitors (e.g., alpha1-antitrypsin, TIMP, and alpha2–macroglobulin) to these wounds. As expected, a greater correlation level was observed between the proteases (MMP-8 vs. elastase corr. 0.362 p = 0.097; MMP-8 vs. MMP-9 corr. 0.55 p = 0.009). The results from this study highlight the high degree of variability that can be observed in the pressure ulcer environment. This further suggests that a combination of biomarkers will be required for making accurate diagnostic assessments of chronic wounds. This work was supported by NIH GM 58530.