DIFFERENTIAL EXPRESSION OF PLASMINOGEN ACTIVATORS AND THEIR INHIBITORS IN AN ORGANOTYPIC SKIN COCULTURE SYSTEM

Using immunohistochemistry and in situ hybridization, we have characte rized the expression and localization of components of the plasminogen activator proteolytic cascade in an organotypic coculture system whic h consists of a ''dermal'' portion (human dermal fibroblasts throughou t a collagen matrix) and a stratified, well-differentiated epidermal p ortion. Specifically, the following components were examined: the enzy mes urokinase-type plasminogen activator and tissue-type plasminogen a ctivator and their type 1 and type 2 inhibitors. Urokinase plasminogen activator mRNA and antigen were found predominantly in the least diff erentiated, basal keratinocytes; in some fields there was also faint d eposition of antigen beneath the basal cells. The distribution of plas minogen activator inhibitor type 1 was similar to that of urokinase, e xcept that inhibitor type 1 antigen deposition beneath the basal cells appeared more intense and uniform. In contrast to the results with ur okinase plasminogen activator and inhibitor type 1, tissue plasminogen activator mRNA and antigen were localized focally in the suprabasal, i.e. more differentiated, keratinocytes. Plasminogen activator inhibit or type 2 mRNA and antigen were detected in most epidermal layers, but were more intense suprabasally and often spared the basal layer. Thes e studies demonstrate that the same type of cell, i.e. the keratinocyt e, can express different components of the plasminogen activator casca de depending on its state of differentiation. The change in expression of plasminogen activator cascade components with keratinocyte differe ntiation suggests distinct epidermal functions for these components, r elated to cell-matrix interaction and epidermal differentiation.