Human autoantibodies against desmosomes: possible causative factors in pemphigus.
Human autoantibodies against desmosomes: possible causative factors in pemphigus.
复制标题
抗桥粒的人类自身抗体：天疱疮的可能致病因素。
DOI：
10.1073/pnas.81.9.2781
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发表时间：
1984
影响因子：
11.1
通讯作者：
Goldman,RD
中科院分区：
文献类型：
--
作者：
Jones,JC;Arnn,J;Staehelin,LA;Goldman,RD
天疱疮是一种导致皮肤大面积起泡的人类疾病。这种起泡与表皮细胞凝聚力的丧失有关，并伴有循环自身抗体对表皮细胞表面进行染色，如免疫荧光显微镜所示。参与表皮细胞凝聚的主要成分之一是桥粒。天疱疮伴随的病理变化使我们确定自身抗体是否对桥粒具有特异性。在含有天疱疮抗血清的培养基中培养培养的小鼠角质形成细胞，导致细胞在具有桥粒的细胞-细胞接触位点分离。使用针对桥粒成分的天疱疮抗血清或兔抗血清对小鼠皮肤的组织切片进行间接免疫荧光处理，显示出表皮内类似的点状细胞表面染色模式。使用针对小鼠皮肤角蛋白的单克隆抗体以及天疱疮抗血清或桥粒抗血清，对具有明确的中间丝束（张力丝）和桥粒的培养的小鼠角质形成细胞进行双重间接免疫荧光处理。角质形成细胞表现出包含角蛋白的张力丝的复杂系统。接触细胞中的张力丝被细胞表面的细暗带分开，这与相差显微镜观察到的桥粒斑块精确对应。这些条带用天疱疮抗血清和桥粒抗血清特异性染色。使用天疱疮抗血清和桥粒抗血清对培养的小鼠角质形成细胞进行双重间接免疫荧光显示，天疱疮自身抗体对与桥粒抗体相同的细胞-细胞接触区域进行染色。我们的证据支持天疱疮水泡形成的观点，至少部分是由特定抗体诱导的表皮桥粒破坏形成的。
Pemphigus is a human disease that causes extensive blistering of the skin. This blistering is related to a loss of epidermal cell cohesion and is accompanied by circulating autoantibodies that stain epidermal cell surfaces, as shown by immunofluorescence microscopy. One of the major components involved in epidermal cell cohesion is the desmosome. The pathological changes that accompany pemphigus led us to determine whether the autoantibodies are specific for desmosomes. Incubation of cultured mouse keratinocytes in medium containing pemphigus antiserum leads to cell separation at cell-cell contact sites, which possess desmosomes. Tissue sections of mouse skin processed for indirect immunofluorescence, using pemphigus antiserum or a rabbit antiserum directed against components of desmosomes, show similar punctate cell-surface staining patterns within the epidermis. Cultured mouse keratinocytes possessing well-defined intermediate filament bundles (tonofilaments) and desmosomes were processed for double indirect immunofluorescence, using a monoclonal antibody directed against mouse skin keratin and either pemphigus antiserum or the desmosome antiserum. The keratinocytes exhibit a complex system of keratin-containing tonofilaments. Tonofilaments in contacting cells are separated by thin dark bands at the cell surface, which correspond precisely to desmosomal plaques seen by phase-contrast microscopy. These bands specifically stain with both pemphigus antiserum and the desmosome antiserum. Double indirect immunofluorescence of the cultured mouse keratinocytes, using pemphigus antiserum and the desmosome antiserum, reveals that the pemphigus autoantibodies stain the same areas of cell-cell contact as the desmosome antibodies. Our evidence supports the idea that pemphigus blisters form, at least in part, from a specific antibody-induced disruption of desmosomes in the epidermis.