Serum is a potent stimulator of keratinocyte tissue plasminogen activator expression

The plasminogen activator (PA) proteolytic cascade comprises two enzymes known as urokinase PA (uPA) and tissue PA (tPA), both of which activate plasminogen to plasmin. In normal human epidermis uPA is the predominant PA. In lesional epidermis from patients with a variety of cutaneous diseases, including psoriasis, pemphigus foliaceous, pemphigus, vulgaris, bullous pemphigoid, and benign chronic pemphigus, however, tPA is selectively elevated and becomes the predominant PA activity. The enhanced tPA is likely to be a reaction to the disease challenge rather than an initiating event in these clinically and etiologically diverse lesions. In the present study, cultured human keratinocytes, propagated under serum-free conditions, have been shown to respond to the addition of bovine or human serum with an increase in tPA activity and antigen. Furthermore, tPA is found predominantly in the suprabasal keratinocytes both in lesional epidermis and in stratified cultures that have been incubated for approximately 8 d in the presence of serum. These results suggest a possible mechanism by which epidermal tPA may be increased in diverse cutaneous lesions: The plasma infiltrated into lesional epidermis may stimulate the suprabasal keratinocytes in vivo to express tPA.