Herouet C, Cottin M, LeClaire J, Enk A, Rousset F
Clinical Research Unit, Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany.
In Vitr Mol Toxicol. 2000 Summer;13(2):113-23. doi: 10.1089/109793300440703.
Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.
接触性敏感是一种由T细胞介导的免疫疾病，当低分子量化学物质穿透皮肤时可能会发生。在体内局部应用化学致敏剂会导致朗格汉斯细胞（LC）的形态改变。此外，在18小时内，LC会增加其主要组织相容性复合体（MHC）II类抗原的表达，并迁移至淋巴结，在那里它们将致敏剂呈递给T淋巴细胞。我们想确定在体外是否也能观察到这种效应。然而，由于人类存在高度的遗传多样性，因此使用从Balb/c小鼠品系获得的树突状细胞（DC）进行了实验。研究了强致敏剂2,4-二硝基苯磺酸（DNBS）在体外调节骨髓来源DC表型的能力。在18小时内观察到MHC II类分子表达有特异性且显著的增加。为了在致敏研究中避免使用动物，对未成熟阶段的XS52 DC系进行了测试。与强致敏剂DNBS和恶唑酮或中度致敏剂巯基苯并噻唑接触30分钟后，在孵育18小时后分析发现MHC II类分子表达上调。刺激性物质（二甲基亚砜和十二烷基硫酸钠）以及中性分子（氯化钠）未观察到这种效应。这些数据表明，有可能利用一种恒定且不消耗动物的材料开发一种体外模型，用于鉴定化学物质的致敏潜力。
