Haftek M, Kowalewski C, Mesnil M, Blaszczyk M, Schmitt D
INSERM U.346/CNRS 'Human Skin and Immunity', Hôpital E.Herriot, 69437 Lyon cedex 03, France.
Br J Dermatol. 1999 Aug;141(2):224-30. doi: 10.1046/j.1365-2133.1999.02969.x.
Hereditary skin disorders involving acantholysis, such as Hailey-Hailey disease and Darier's disease, have been genetically linked to distinct chromosomal parts which do not code for known structural proteins. Such evidence suggests that the genomic abnormalities underlying these dermatoses may concern functional/regulatory mechanisms of keratinocyte cohesion. Epidermal communication junctions (gap junctions) are responsible for direct coupling of cells and, thus, co-ordinate the behaviour of keratinocytes within the tissue. Consequently, they remain one of the potential, and poorly studied, elements in the pathogenesis of hereditary acantholytic diseases. We have investigated the distribution and fate of gap junctions during non-immune acantholysis, using fine immunolocalization methods at the light and electron microscopic levels. Our results demonstrate normal expression of epidermal gap junction proteins, connexins 26 and 43, in non-lesional skin of Hailey-Hailey and Darier's diseases. The gap junctions were not primarily dismantled during acantholysis, typical of both of the studied dermatoses, but underwent internalization and subsequent cytoplasmic dispersion in the portions of cells which were no longer attached to the rest of the tissue. In Darier's disease, perifollicular acantholysis did not specifically concern epithelium of appendages coexpressing connexin 26 in addition to connexin 43, further indicating that the observed changes in gap junction localization were secondary to the loss of cell-cell contact. We demonstrated that the sequence of changes was identical in both diseases and that the previously described putative differences were apparently related to the degree of acantholysis present in the studied biopsies. The fate of the junctional structures and proteins, documented in the present study, is most probably a form of recycling process also used by normal keratinocytes during organogenesis and tissue differentiation.
涉及棘层松解的遗传性皮肤病，如黑利-黑利病和毛囊角化病，在基因上与不编码已知结构蛋白的不同染色体部分相关联。这些证据表明，这些皮肤病潜在的基因组异常可能与角质形成细胞黏附的功能/调节机制有关。表皮通讯连接（缝隙连接）负责细胞间的直接耦联，从而协调组织内角质形成细胞的行为。因此，它们仍然是遗传性棘层松解性疾病发病机制中潜在且研究较少的因素之一。我们利用光镜和电镜水平的精细免疫定位方法，研究了非免疫性棘层松解过程中缝隙连接的分布和命运。我们的结果表明，在黑利-黑利病和毛囊角化病的非皮损皮肤中，表皮缝隙连接蛋白连接蛋白26和43表达正常。在所研究的两种皮肤病典型的棘层松解过程中，缝隙连接并非首先被拆解，而是在不再与组织其余部分相连的细胞部分发生内化并随后在细胞质中分散。在毛囊角化病中，毛囊周围棘层松解并非特异性地涉及除连接蛋白43外还共表达连接蛋白26的附属器上皮，这进一步表明观察到的缝隙连接定位变化是细胞间接触丧失的继发结果。我们证明，两种疾病中变化的顺序相同，并且先前描述的假定差异显然与所研究活检标本中棘层松解的程度有关。本研究记录的连接结构和蛋白的命运很可能是正常角质形成细胞在器官发生和组织分化过程中也使用的一种回收过程形式。
