Research on the mechanism of bullous diseases-Immunological and biological studies-

我们对皮肤基底膜带（BMZ）的功能和结构以及自身免疫性大疱病的发病机制进行了研究。我们对其他器官（如粘膜等）BMZ的发病机制的解决作出了贡献。我们得到的水果如下。(1)信号转导的研究。据报道，天疱疮IgG结合角质形成细胞可能发挥跨膜信号作用。我们报道了大疱性类天疱疮（BP）患者的IgG诱导细胞内Ca^<2+>浓度（[Ca^<2+>]i）的短暂增加，并通过添加磷脂酶C抑制剂抑制这种增加（自身免疫，1996）。这些结果提示BP IgG结合角质形成细胞可能发挥跨膜信号作用。(2) IgG亚类在BP发病机制中的作用研究：我们报道BP IgG_1主要诱导[Ca^<2+>]i的一过性升高，BP IgG_2和IgG_4抑制BP IgG_1诱导的[Ca^<2+>]i的升高（Autoimmunity, 1996 and submitted）。据报道，在天疱疮中观察到IgG亚类的转换，并且IgG_4可能作为阻断抗体。另一方面，我们报道BP中IgG亚类切换的可能性很低（已提交）。在BP中，IgG亚型主要为IgG_1和IgG_4。抗bmz抗体IgG滴度与抗bmz抗体IgG_1和IgG_4呈正相关。(3) BMZ结构研究。我们检查了BMZ的起源硫酸软骨素蛋白多糖的BMZ真皮-表皮交界处和毛囊上皮是表皮起源（j.j.d., 1996）。然后，我们为解决与迟发性肌肉萎缩症相关的大疱性表皮松解症的发病机制做出了贡献（人类分子遗传学，1996）。(4)口腔粘膜细胞粘附分子的研究。应用免疫组织化学方法检测了黏附分子在正常口腔黏膜、舌和牙龈中的表达和定位。整合素α 5仅在粘膜中检测到，而在舌头和牙龈中未检测到（口腔肿瘤学，1995）。整合素alpha2、alpha3、alpha6、beta1、beta3、beta4以及E-cadherin、P-cadherin、粘胶蛋白、ICAM-1在粘膜、舌部和龈部的分布无明显变化。少

We have been studied the function and structure of cutaneous basement membrane zone (BMZ), and the pathogenesis of autoimmune bullous diseases. We have been contributed to the solution of the pathogenesis of the disease on BMZ of the other organs (ex.mucous membrane etc.). We get the fruits as follows. (1) The study of signal transduction. It was reported the possibility of transmembrane signalling exerted by pemphigus IgG binding keratinocytes. We reported a transient increase of intracellular Ca^<2+> concentration ( [Ca^<2+>]i) induced by IgG from the patients with bullous pemphigoid (BP), and the inhibition of this increase by the addition of phospholipase C inhibitor (Autoimmunity, 1996). These results suggested the possibility of transmembrane signaling exerted by BP IgG binding keratinocyte. (2) The study of the role of IgG subclass in the pathogenesis of BP : We reported that BP IgG_1 mainly in duce a transient in crease of [Ca^<2+>]i, and BP IgG_2 and IgG_4 inhibit an increase … More of [Ca^<2+>]i induced by BP IgG_1 (Autoimmunity, 1996 and submitted). In pemphigus, it was reported that a switching of IgG subclass was observed, and the possibility that IgG_4 serves as blocking antibody. On the other hand, we reported that there was a low possibility of IgG subclass switching in BP (submitted). In BP,the main IgG subclass were IgG_1 and IgG_4. The anti-BMZ autibody IgG titer was correlated with anti-BMZ IgG_1 and IgG_4. (3) The study of structure of BMZ.We examined the origins of BMZ chondroitin sulfate proteoglycan of BMZ of dermal-epidermal junction and hair follicle epithelium are of epidermal origin (J.J.D., 1996). Then we contributed to the solution of the pathogenesis of epidermolysis bullous simplex associated with late-onset muscular dystrophy (Human Molecular Genetics, 1996). (4) The study of cell adhesion molecule in oral mucous membrane. We examined the expression and localization of adhesion molecules in human normal oral mucous, tongue and gingiva, immunohistochemically. Integrin alpha5 was detected only in mucous membrane but not in tongues and gingiva (Oral oncology, 1995). The distribution of integrin alpha2, alpha3, alpha6, beta1, beta3 and beta4, and E-cadherin, P-cadherin, desmoglain and ICAM-1 was no significant change among mucous membrane, tongue and gingiva. Less