Pemphigus is a severe, blistering disease of the skin and mucous membranes. There is loss of epidermal cohesion manifested clinically by induction of intraepidermal blisters and erosions with mechanical trauma (Nikolski's sign). Biopsies of lesional skin reveal rounding up of epidermal cells with loss of epidermal cell adhesion: this pattern is referred to as acantholysis. Two major types of pemphigus are distinguished clinically and histopathologically. Pemphigus vulgaris exhibits extensive erosions and the vesicles form just above the basal layer of epidermal cells. In contrast, pemphigus foliaceous has very shallow blisters that appear in the more superficial granular layer of the epidermis.In 1964, Beutner and Jordan (1) demonstrated that serum from pemphigus patients contained autoantibodies that bound to an intercellular substance of skin and mucosa. Skin biopsies revealed in vivo deposition of autoantibodies in the epidermis of pemphigus patients (2). Recently, immunoflorescence techniques have shown that pemphigus antibody binds to the surface of mouse epidermal cells (3-5), human epidermal ceils (5, 6), squamous cell carcinoma lines (7,8), and a cervical carcinoma cell line (K. Singer, unpublished results).Michel and Ko (9) reported that incubation of pemphigus antibody with organ cultures of normal human skin resulted in histologic changes identical to those seen in biopsies of skin from pemphigus patients. Schiltz and Michel (10) showed that the IgG fraction of serum was responsible for loss of cellular adhesion in a complementindependent manner.Our laboratory (3) presented evidence that a proteinase was responsible for the * Publication 130 of the Dermatological Research

Primary cultures of human epidermal cells produce plasminogen activator (PA) as demonstrated by the ability of conditioned medium or cell lysates to hydrolyze fibrin in the presence of plasminogen, and to cleave [125I]plasminogen to characteristic fragments. The major molecular species of PA in human epidermal cells was inhibited by diisopropylfluorophosphate and comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the high molecular weight band of human urokinase (Mr 55,000). Production of PA by human epidermal cells was inhibited by cycloheximide, stimulated by colchicine, and not affected by cytochalasin B or the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. Both cholera toxin and epidermal growth factor stimulated PA activity in human epidermal cells, and PA activity was maximal at concentrations that best support in vitro growth of human epidermal cells. Examination of individual cells indicated that at least 15% of cells within a culture produced detectable amounts of PA.