Pemphigus IgG induces expression of urokinase plasminogen activator receptor on the cell surface of cultured keratinocytes

We previously found that the binding of pemphigus IgG to desmogleins caused marked activation of phospholipase C, a transient increase in inositol 1,4,5-trisphosphate production, and a concomitant increase in the intracellular calcium concentration in DJM-1 cells, a squamous cell carcinoma line, The binding of pemphigus IgG to cell membranes increased the activity of urokinase plasminogen activator in culture medium and induced subsequent cell-cell detachment in DJM-1 cells, Because urokinase plasminogen activator activates the conversion of plasminogen to plasmin by binding to urokinase plasminogen activator receptor evading inhibitors in serum, it is Likely that plasmin is generated only in microenvironments adjacent to urokinase plasminogen activator receptor on the cell surface, It is not known whether pemphigus IgG causes acantholysis by inducing urokinase plasminogen activator receptor expression on the cell surface and secreting urokinase plasminogen activator in inhibitor-rich environments, We examined the effects of pemphigus IgG on urokinase plasminogen activator receptor expression in DJM-1 cells and normal keratinocytes by immunoblot analysis and immunofluorescence microscopy using antibodies to urokinase plasminogen activator receptor, IgG were obtained from serum samples from eight patients with bullous pemphigoid, five patients with pemphigus vulgaris, seven patients with pemphigus foliaceus, and eight normal subjects, Pemphigus vulgaris and pemphigus foliaceus IgG significantly increased the urokinase plasminogen activator receptor expression on the surface of DJM-1 cells and normal keratinocytes after 3- and 7-d incubation compared with normal IgG. These results suggest that enhanced urokinase plasminogen activator activity and urokinase plasminogen activator receptor expression activates plasmin in the limited tell surface of pemphigus IgG-bound keratinocytes and may contribute to the pathogenesis of differential acantholysis in pemphigus vulgaris and pemphigus foliaceus.