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

寻常天疱疮（PV）是一种自身免疫性皮肤病，其特征在于针对桥粒芯糖蛋白3的自身抗体。虽然PV-IgG与角质形成细胞结合诱导皮肤起泡的确切机制尚未阐明，但天疱疮IgG诱导的棘层松解可能是由角质形成细胞的蛋白酶如纤溶酶原激活剂引起的。我们已经研究了PV-IgG对细胞内信号转导事件的影响，并证明PV-IgG与DJM-1细胞（鳞状细胞癌细胞系）结合诱导磷脂酶C活化的瞬时增加，以及增加的肌醇1，4，5-三磷酸生产，伴随着细胞内钙浓度的增加。这些事件与纤溶酶原激活剂分泌到培养基中以及随后的细胞-细胞分离直接相关。此外，在PV-IgG暴露后，颗粒/细胞骨架部分中的蛋白激酶C（PKC）活性增加，在1分钟时达到峰值，这些结果表明，PKC的激活模式可能参与介导细胞内信号转导在培养的人角质形成细胞中PV-IgG与桥粒芯糖蛋白3结合诱导的事件。

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.