Antipsoriatic therapies inhibit epidermal plasminogen activator activity

Urokinase (UK, Mr 55,000) and tissue-type plasminogen activator (tPA, Mr 74,000) are serine proteinases involved in many biological processes, ie, cell migration, neoplastic transformation, and extracellular proteolysis. Cutaneous fibrinolytic activity (dependent on the activity of UK and tPA) was studied with the autohistographic fibrin film method in 40 patients affected by psoriasis vulgaris before and after topical (anthralin, betamethasone valerate, hydrocolloid occlusive dressing) or systemic psoralen-ultraviolet-light (PUVA) treatments. Autohistographic studies also were performed after apposition of monoclonal antibodies directed against the catalytic site of UK and tPA. Finally, UK and tPA were localized immunohistochemically in the psoriatic plaques and in controls using the immunoperoxidase procedure based on the biotin/avidin system. UK and tPA immunoreactivity was present in the cytoplasm and around the outlines of keratinocytes in the psoriatic patches before treatment and in the patches not cleared after treatment, while it was not detectable in normal epidermis, in the unaffected psoriatic epidermis, and in the cleared psoriatic skin. Cutaneous fibrinolytic activity was present in the cases in which UK and tPA were detected histochemically and, in the psoriatic epidermis, it was abolished by preincubation with anti-tPA but not with anti-UK antibodies. This study suggests that established topical and systemic treatments for psoriasis possess UK and tPA antagonist activity.