IgG from Patients with Bullous Pemphigoid Depletes Cultured Keratinocytes of the 180-kDa Bullous Pemphigoid Antigen (Type XVII Collagen) and Weakens Cell Attachment
IgG from Patients with Bullous Pemphigoid Depletes Cultured Keratinocytes of the 180-kDa Bullous Pemphigoid Antigen (Type XVII Collagen) and Weakens Cell Attachment
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DOI：
10.1038/jid.2008.305
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Kitajima, Yasuo
中科院分区：
文献类型：
--
作者：
Iwata, Hiroaki;Kamio, Naoko;Kitajima, Yasuo
我们已经表明，大疱性类天疱疮（BP）患者IgG（BP-IgG）的结合导致BP 180从细胞膜内化。该研究检查了BP-IgG治疗是否可以耗尽培养的角质形成细胞的BP 180，它如何影响α 6和β 4整联蛋白的细胞水平（通过使用针对这些抗原的单克隆抗体的蛋白质印迹分析），以及它是否减少细胞对培养皿的粘附（通过振动分离测定）。所有BP-IgG或BP血清与高值的BP 180-ELISA从18 BP患者口服皮质类固醇治疗前后显示显着降低BP-IgG刺激后6小时的细胞中的BP 180，而α 6和β 4整合素水平没有降低。甚至口服皮质类固醇抑制活性水疱的患者的IgG也可以耗尽BP 180细胞，只要血清保留高值的BP 180-ELISA。另一方面，细胞BP 180含量的减少增加了细胞从培养皿的脱离。这些结果表明，BP-IgG减少半桥粒BP 180含量，减弱半桥粒对致密板的粘附。在存在BP 180缺陷的情况下，由BP 180免疫复合物形成产生的炎症然后可能撕裂弱化的透明板，并且这可能导致在透明板处产生BP特异性分裂。
We have shown that binding of bullous pemphigoid (BP)-patient IgG (BP-IgG) causes the internalization of BP180 from the cell membrane. This study examined whether BP-IgG treatment can deplete cultured keratinocytes of BP180, how it affects cellular levels of alpha 6 and beta 4 integrins (by western blot analysis using monoclonal antibodies to these antigens), and whether it reduces adhesion of cells to the culture dish (by a vibration detachment assay). All BP-IgG or BP sera with high values of BP180-ELISA from 18 BP patients before and after oral corticosteroid treatment showed dramatically decreased BP180 in cells after 6 hours of BP-IgG stimulation, whereas a6 and b4 integrin levels were not decreased. Even IgG from patients in whom oral corticosteroid had suppressed active blistering could deplete cells of BP180, as long as sera retained a high value of BP180-ELISA. On the other hand, reduction of cell BP180 content increased detachment of cells from the dish. These results suggest that BP-IgG reduces hemidesmosomal BP180 content, weakening the adhesion of hemidesmosomes to the lamina densa. In the presence of BP180 deficiency, inflammation generated by BP180 immune-complex formation might then tear the weakened lamina lucida, and this could lead to generation of the BP-specific split at the lamina lucida.