Lehé Cynthia L, Jacobs John J L, Elliott Graham R, Das Pranab K
Department of Pathology, UvA-AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Altern Lab Anim. 2003 Dec;31(6):553-61. doi: 10.1177/026119290303100604.
Animal models are considered to be the "gold standard" for determining the potential contact allergenicity of low molecular weight chemicals. However, governmental regulations and ethical considerations limit the use of animals for such purposes. There is therefore a need for in vitro alternative models. The human organotypic skin explant culture (HOSEC) model is reported to be a promising alternative method for the predictive testing of contact allergens. The accelerated migration of Langerhans cells from the epidermis upon exposure to contact allergens is used to identify chemicals that are potentially capable of inducing a delayed-type hypersensitivity. In the study described in this paper, the model was further refined, and used, in two independent laboratories, to screen 23 low molecular weight compounds of known classification for their allergenicity. Each laboratory was able to accurately detect the contact allergens, despite small variations in the protocols used. However, the classification of dermal irritants, which have often been falsely classified as allergens, varied between the two laboratories. Despite the current limitations of the HOSEC model, the accuracy of the predictions made (sensitiser or non-sensitiser) compare favourably with classifications obtained with commonly used animal models. The HOSEC model has the potential to be developed further as an in vitro alternative to animal models for screening for contact allergens.
动物模型被认为是确定低分子量化学物质潜在接触致敏性的“金标准”。然而，政府法规和伦理考量限制了将动物用于此类目的。因此，需要体外替代模型。据报道，人器官型皮肤外植体培养（HOSEC）模型是一种用于接触性变应原预测性测试的有前景的替代方法。暴露于接触性变应原时，朗格汉斯细胞从表皮加速迁移，用于识别可能能够诱导迟发型超敏反应的化学物质。在本文所述的研究中，该模型得到了进一步完善，并在两个独立实验室中用于筛选23种已知分类的低分子量化合物的致敏性。尽管使用的方案存在细微差异，但每个实验室都能够准确检测出接触性变应原。然而，经常被错误分类为变应原的皮肤刺激性物质的分类在两个实验室之间有所不同。尽管HOSEC模型目前存在局限性，但所做预测（致敏剂或非致敏剂）的准确性与常用动物模型获得的分类结果相比具有优势。HOSEC模型有潜力进一步发展成为一种体外替代动物模型，用于筛选接触性变应原。
