Signal Transduction Induced by Desmosomal Cadherin Antigen-Antibody Reaction in Bullous Formation in Pemphigus

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Pemphigus vulgaris (PV) is an autoimmune skin disease characterized by the autoantibodies against desmoglein 3. Although the exact mechanism for cutaneus blistering induced by PV-IgG binding to keratinocytes has not yet elucidated, pemphigus IgG-induced acantholysis may be caused by proteinases from keratinocytes such as plasminogen activator. We have studied the effects of PV-IgG on the intracellular signal transduction events, and demonstrated that PV-IgG-binding to DJM-1 cells (a squamous cell carcinoma line) induces a transient increase in phospholipase C activation, and an increased inositol 1,4,5-trisphophate production, with a concomitant increase in intracellular calcium concentration. These events are directly associated with secretion of plasminogen activator into the culture medium, and subsequent cell-cell detachment.In addition, the protein kinase C (PKC) activity in the particulate/cytoskeleton fraction was increased following PV-IgG exposure, peaking at 1 min, and being sustained for at leaset 30 min. These findings suggest that an activation profile of PKC may be involvedin mediationg the intracellular signaling events induced by PV-IgG binding to desmoglein 3 in cultured human keratinocytes.