Parish W E
Food Chem Toxicol. 1986 Jun-Jul;24(6-7):481-94. doi: 10.1016/0278-6915(86)90098-0.
Investigations of in vitro procedures to predict the potential of substances as skin irritants and as allergens inducing delayed hypersensitivity (contact dermatitis) are described, with indications of possible advances and known limitations. The examination of keratome slices of skin for release of enzymes, for changed histochemistry and for utilization of radioisotope-labelled amino acids will detect weak irritants but is of doubtful value for moderate irritants and will detect corrosive substances only through their inhibition of all cell activities. Fibroblast cultures, tested with Clostridium perfringens toxin and chemicals, show similar limitations in detecting moderate or severe irritants. Fibroblast cultures can be made more relevant to epidermal exposure by an overlying layer of agar containing keratin. In vitro tests to detect induction of sensitizing potential for delayed hypersensitivity have made little progress. The most promising approach is to treat antigen-presenting Langerhans cells with antigen and co-culture with lymphocytes. The lymphocytes may be examined for changes in receptor expression, for synthesis of interleukin 2, and possibly for responses to allergen if sufficient cells become specifically sensitized. There are several in vitro techniques to detect responses of in vivo- or in vitro-sensitized lymphocytes treated with antigen.
本文描述了预测物质作为皮肤刺激物和诱导迟发型超敏反应(接触性皮炎)的变应原潜力的体外实验方法,并指出了可能的进展和已知的局限性。通过检测皮肤角质切片中酶的释放、组织化学变化以及放射性同位素标记氨基酸的利用情况,能够检测出弱刺激物,但对于中度刺激物的检测价值存疑,且仅能通过其对所有细胞活动的抑制作用来检测腐蚀性物质。用产气荚膜梭菌毒素和化学物质检测成纤维细胞培养物,在检测中度或重度刺激物时也存在类似局限性。通过覆盖一层含角蛋白的琼脂,可使成纤维细胞培养物与表皮暴露情况更具相关性。用于检测迟发型超敏反应致敏潜力诱导的体外试验进展甚微。最有前景的方法是用抗原处理抗原呈递朗格汉斯细胞,并与淋巴细胞共培养。可检测淋巴细胞受体表达的变化、白细胞介素 2 的合成情况,如果有足够的细胞发生特异性致敏,还可能检测其对变应原的反应。有几种体外技术可检测经抗原处理的体内或体外致敏淋巴细胞的反应。