Characterization of keratinocyte plasminogen activator inhibitors and demonstration of the prevention of pemphigus IgG-induced acantholysis by a purified plasminogen activator inhibitor.

To investigate the mechanisms by which cutaneous plasminogen activator (PA) may be regulated, we have tested cultured keratinocytes for the presence of PA inhibitors. Using biosynthetic labeling experiments with 35S-methionine in conjunction with specific antibody precipitation, we have shown that human keratinocytes in culture synthesized and secreted both PA inhibitor 1 and PA inhibitor 2. PA inhibitor 1 was present in conditioned media in the inactive form, but it could be detected with reverse phase autography. PA inhibitor 2 was detected by its ability to form complexes with 125I-uPA. Potential therapeutic relevance for cutaneous PA inhibitor 2 was suggested in skin organ culture experiments which demonstrated that purified PA inhibitor 2 from human placenta was able to prevent the acantholytic changes induced by pemphigus IgG.