Tada J, Hashimoto K
Department of Dermatology, Okayama University Medical School, Shikata, Japan.
J Cutan Pathol. 1998 Feb;25(2):106-15. doi: 10.1111/j.1600-0560.1998.tb01698.x.
The distribution of desmoglein, plakoglobin, E-cadherin, and beta-catenin in the peri-lesional and lesional skin of Hailey-Hailey disease, Darier's disease, and pemphigus vulgaris was examined by immunoelectron microscopy. In the peri-lesional skin, the immunolabeling of these desmosomal components was localized to desmosomes. Adherens junction-associated E-cadherin and beta-catenin were at the cell periphery, excluding desmosomes. The labeling pattern was similar among these diseases, but the labeling intensity particularly that of plakoglobin in Hailey-Hailey disease and Darier's disease, was less than that of normal controls, suggesting that these glycoproteins are quantitatively less concentrated in the normal epidermis of these inherited diseases. In the acantholytic cells of Hailey-Hailey disease and Darier's disease the immunolabeling of the components of desmosomes was diffusely distributed in the cytoplasms, whereas that of adherensjunction was mostly at the cell periphery and partly diffusely in the cytoplasm. In contrast, desmosomes of detaching keratinocytes in pemphigus vulgaris still showed the labeling of desmoglein and plakoglobin. These findings suggest that the inherited acantholytic diseases, i.e., Hailey-Hailey disease and Darier's disease have a different pathogenesis from that of autoimmune acantholysis in pemphigus vulgaris: The intracellular components of desmosomes may primarily be disrupted in the genetic acantholytic diseases in the initial stages of acantholysis. Several unsolved questions in the previous light microscopic immunofluorescence studies using the same antibodies are now answered: 1) the diffusion of desmosomal proteins is not due to the internalization of desmosomes, 2) intracellular components of adherens junction are also finally dissolved, 3) diffuse cytoplasmic immunofluorescence patterns of desmosomal components could be explained by immunoelectron microscopy as those attached to cell membrane and trapped in tonofilament aggregates.
采用免疫电子显微镜检查了Hailey-Hailey病、毛囊角化病和寻常型天疱疮的病损周围皮肤及病损皮肤中桥粒芯糖蛋白、桥粒斑珠蛋白、E-钙黏蛋白和β-连环蛋白的分布情况。在病损周围皮肤中，这些桥粒成分的免疫标记定位于桥粒。黏附连接相关的E-钙黏蛋白和β-连环蛋白位于细胞周边，不包括桥粒。这些疾病之间的标记模式相似，但Hailey-Hailey病和毛囊角化病中桥粒斑珠蛋白的标记强度，尤其是其标记强度低于正常对照，提示这些糖蛋白在这些遗传性疾病的正常表皮中定量分布较少。在Hailey-Hailey病和毛囊角化病的棘层松解细胞中，桥粒成分的免疫标记弥散分布于细胞质中，而黏附连接的免疫标记大多位于细胞周边，部分弥散于细胞质中。相比之下，寻常型天疱疮中正在分离的角质形成细胞的桥粒仍显示桥粒芯糖蛋白和桥粒斑珠蛋白的标记。这些发现提示，遗传性棘层松解疾病，即Hailey-Hailey病和毛囊角化病与寻常型天疱疮的自身免疫性棘层松解具有不同的发病机制：在棘层松解的初始阶段，桥粒的细胞内成分在遗传性棘层松解疾病中可能首先受到破坏。先前使用相同抗体进行的光镜免疫荧光研究中几个未解决的问题现在得到了解答：1）桥粒蛋白的弥散并非由于桥粒的内化；2）黏附连接的细胞内成分最终也会溶解；3）桥粒成分的弥漫性细胞质免疫荧光模式可通过免疫电子显微镜解释为附着于细胞膜并被困于张力丝聚集体中。
