Involvement of proteolytic enzymes--plasminogen activators and matrix metalloproteinases--in the pathophysiology of pressure ulcers.

The role of matrix-degrading enzymes, particularly plasminogen activators and matrix metalloproteinases, in the acute wound healing response has been the focus of many scientific studies. Only recently have these classes of endogenously produced proteinases been studied with regard to their involvement in the chronic wound environment. Using both in situ histologic zymography and immunohistochemical techniques, we examined the distribution of plasminogen activators and matrix metalloproteinase in the granulation tissue of pressure ulcers. Using in situ histologic zymography, urokinase was found to be the predominant plasminogen activator activity in the chronic wound granulation tissue, with little or no tissue-type plasminogen activator activity. These results were confirmed with the use of immunohistochemical techniques. In contrast, tissue-type plasminogen activator was found to be constitutively expressed in normal skin. Levels of matrix metalloproteinases were also found to be elevated in the granulation tissue of pressure ulcers. Immunohistochemical localization of leukocyte-associated proteinases (PMN elastase and cathepsin G) suggested a highly inflamed environment within the pressure ulcer granulation tissue. These results suggest a highly proteolytic environment within the chronic wound.