Aleksic Maja, Thain Emma, Gutsell Stephen J, Pease Camilla K, Basketter David A
Safety & Environmental Assurance Centre Unilever Colworth, Sharnbrook, Bedfordshire.
Cutan Ocul Toxicol. 2007;26(2):161-9. doi: 10.1080/15569520701212282.
Skin sensitisation is a delayed hypersensitivity reaction caused by repeated exposure to common natural and synthetic chemical allergens. It is thought that small chemical sensitisers (haptens) are required to form a strong irreversible bond with a self protein/peptide and generate an immunogenic hapten-protein complex in order to be recognised by the immune system and stimulate T cell proliferation. The sensitisers are usually electrophilic chemicals that are directly reactive with proteins or reactive intermediates (metabolites) of chemically inert compounds (prohaptens). Sensitising chemicals are also capable of weak, non-covalent association with proteins and there is an ongoing debate about the role of weak interactions of chemicals and proteins in the chemistry of allergy. The non-covalent interactions are reversible and thus have a major impact on skin/epidermal bioavailability of chemical/reactive metabolites. We investigated the relationship between the relative level of non-covalent association to a model protein and their relative potencies as determined by the EC3 values in the murine local lymph node assay (LLNA) for a number of chemicals. Using human serum albumin as a model protein, we determined that no observable relationship exists between the two parameters for the chemicals tested. Therefore, at least for this model protein, non-covalent interactions appear not to be a key determinant of allergen potency.
皮肤致敏是一种由反复接触常见天然和合成化学过敏原引起的迟发型超敏反应。据认为，小化学致敏剂（半抗原）需要与自身蛋白质/肽形成牢固的不可逆键，并生成免疫原性半抗原-蛋白质复合物，才能被免疫系统识别并刺激T细胞增殖。致敏剂通常是亲电化学物质，可与蛋白质或化学惰性化合物（前体半抗原）的反应性中间体（代谢物）直接发生反应。致敏化学物质也能够与蛋白质形成弱的非共价结合，关于化学物质与蛋白质的弱相互作用在过敏化学中的作用，目前仍存在争议。非共价相互作用是可逆的，因此对化学物质/反应性代谢物的皮肤/表皮生物利用度有重大影响。我们研究了与模型蛋白的非共价结合相对水平与其在小鼠局部淋巴结试验（LLNA）中由EC3值确定的相对效力之间的关系，涉及多种化学物质。以人血清白蛋白作为模型蛋白，我们确定在所测试的化学物质中，这两个参数之间不存在可观察到的关系。因此，至少对于这种模型蛋白来说，非共价相互作用似乎不是过敏原效力的关键决定因素。
