EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-2 IN NORMAL AND PSORIATIC EPIDERMIS

The plasminogen activator (PA) proteolytic cascade has been implicated in the regulation of cell activities, including proliferation and dif ferentiation, both of which occur continuously in normal human epiderm is and are aberrant in psoriatic epidermis. To elucidate further the m echanisms by which PA is regulated in epidermis, we evaluated the leve ls of PA inhibitors type 1 (PAI-1) and type 2 (PAI-2) in normal and ps oriatic epidermis. PAI-2, but not PAI-1, was detectable by mRNA, antig en, and activity assays, indicating that PAI-2 is the predominant epid ermal PA inhibitor. In situ hybridization revealed that PAI-2 mRNA occ urred throughout normal epidermis, although the signal was most intens e in the granular layers. Similarly, PAI-2 antigen was most prominent in the granular layers; its distribution in these differential layers was along the cell periphery. Diffuse, fainter staining for PAI-2 was also detected in the basal cells and in some spinous layers of normal epidermis. Extracts of normal epidermis contained PA inhibitory activi ty identified as PAI-2 by immunoprecipitation with specific antibody. In psoriatic epidermis, PAI-2 mRNA and antigen were most prominent in the more superficial layers beneath the cornified cells. As with norma l epidermis, PAI-2 assumed a pericellular distribution in the psoriati c cells. These data demonstrate that PAI-2 is constitutively expressed in vivo by keratinocytes in human epidermis and indicate that this pr otein is the predominant inhibitor of PA activity in normal and psoria tic human epidermis.