Differential effects of acute and chronic wound fluids on urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and tissue-type plasminogen activator in cultured human keratinocytes and fibroblasts

The effect of wound fluids collected from acute well-healing wounds and chr onic nonhealing venous leg ulcers on the plasminogen activation system of k eratinocyte and fibroblast cell cultures was studied in a simplified wound- healing model. Acute wound fluid was collected from donor sites of split sk in grafts at different time points representing the progressive healing of the wound, Urokinase-type plasminogen activator, tissue-type plasminogen ac tivator, urokinase-type plasminogen activator receptor, and plasminogen act ivator inhibitor I expression were studied, The methods used were immunocap ture assay and immunocytochemistry, The results indicated that the later th e acute wound fluid was collected, the greater the urokinase-type plasminog en activator and the lower the plasminogen inhibitor-1 level in treated cel ls, In contrast, the level of urokinase-type plasminogen activator receptor remained stable irrespective of wound fluid treatment, Immunostaining for urokinase-type plasminogen activator of acute wound fluid-treated cells sho wed a disseminated punctate pattern over the cell surface, but with chronic wound fluid, urokinase-type plasminogen activator was localized to focal c ontacts, Our findings support the view that in the acute wound environment the plasminogen activator system is proteolytically active and that in chro nic leg ulcers urokinase-type plasminogen activator and urokinase-type plas minogen activator receptor may also be organized for cell adhesion and migr ation.