Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation
Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation
复制标题
抗细胞表面天疱疮自身抗体刺激人表皮细胞的纤溶酶原激活剂活性。
DOI：
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发表时间：
1983
影响因子：
15.3
通讯作者：
Kay H. Singer
中科院分区：
文献类型：
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作者：
Koji Hashimoto;Koji Hashimoto;K. Shafran;P. Webber;Gerald S. Lazarus;Kay H. Singer
抗细胞表面天疱疮自身抗体与培养的人表皮细胞结合可刺激纤溶酶原激活物(PA)的合成和分泌。加入Ig G后6h内PA活性增加，且刺激作用依赖于Ig G。放线菌酮对PA活性的刺激作用受到抑制，说明蛋白质的合成是必要的。药理剂量的地塞米松也可阻止免疫球蛋白G对PA的刺激。培养的人表皮细胞在天疱疮免疫球蛋白存在或不存在的情况下分泌的PA的电泳谱相似。PA的大部分活性与较高相对分子质量的人尿激酶(约55,000种)一起迁移。正常人皮肤的外植体与寻常型天疱疮免疫球蛋白孵育后，显示出与患者活检组织相似的表皮粘附性丧失。组织学变化被人纤溶酶原包涵体所强化。用叶状天疱疮免疫球蛋白孵育的正常皮肤外植体的表皮粘附力的丧失依赖于纤溶酶原的加入，并被抑肽酶或利马豆胰蛋白酶抑制剂抑制，这表明纤溶酶是产生棘层松解的活性酶。这些数据支持这样的假设，即天疱疮的抗细胞表面自身抗体刺激PA会导致纤溶酶的局部增加，而纤溶酶通过蛋白分解导致天疱疮特有的表皮凝聚力的丧失。
Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher- molecular-weight species of human urokinase (approximately 55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characteristic of pemphigus.