Kalergis A M, López C B, Becker M I, Díaz M I, Sein J, Garbarino J A, De Ioannes A E
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago.
J Invest Dermatol. 1997 Jan;108(1):57-61. doi: 10.1111/1523-1747.ep12285632.
Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe contact dermatitis in susceptible human beings. The allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group of allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self proteins which, after proteolytic processing, would generate immunogenic peptides carrying the hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the fatty acid metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the uptake of fatty acids by mitochondria, decreased the hypersensitivity to the hapten. An increase in the level in glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly support a role for the fatty acid oxidative metabolism in the processing and activation of urushiols in vivo.
智利毒漆树（Lithraea caustica），又称“litre”，是漆树科的一种树，原产于智利中部地区，可在易感人群中引发严重的接触性皮炎。此前已分离出该过敏原，并将其鉴定为3 -（十五碳 - 10 - 烯基）邻苯二酚，这是一种属于从毒葛和毒栎植物中分离出的漆酚类过敏原的分子。由于漆酚是亲电半抗原，据信反应性物种是由皮肤角质形成细胞和朗格汉斯细胞在细胞内产生的。活性物种被认为会修饰自身蛋白质，经过蛋白水解处理后，会产生携带半抗原的免疫原性肽。15碳长度的疏水链的存在应会通过空间位阻或限制其分选至内质网腔来损害I类MHC分子对自身修饰肽的抗原呈递。我们提出，过氧化物酶体和/或线粒体内通过β - 氧化缩短脂肪链应该是抗原呈递过程的一个必要条件。为了验证这一假设，我们研究了改变脂肪酸代谢的药物对小鼠漆酚诱导的接触性皮炎的影响。氯贝丁酯是小鼠中的过氧化物酶体增殖剂，可使对来自智利毒漆树的漆酚的免疫反应增加50%。相反，十四烷基缩水甘油酸是线粒体脂肪酸摄取的抑制剂，可降低对半抗原的超敏反应。用2 - 氧代噻唑烷 - 4 - 羧酸处理动物使谷胱甘肽水平升高，降低了反应。这些发现有力地支持了脂肪酸氧化代谢在体内漆酚的加工和激活中的作用。
