Mechanistic Proposal for the Formation of Specific Immunogenic Complexes via a Radical Pathway: A Key Step in Allergic Contact Dermatitis to Olefinic Hydroperoxides
Mechanistic Proposal for the Formation of Specific Immunogenic Complexes via a Radical Pathway: A Key Step in Allergic Contact Dermatitis to Olefinic Hydroperoxides
复制标题
DOI：
10.1021/tx9001435
复制
发表时间：
2009-11-01
影响因子：
4.1
通讯作者：
Borje, Anna
中科院分区：
文献类型：
--
作者：
Johansson, Staffan;Redeby, Theres;Borje, Anna
在当今西方国家，香味产品的广泛使用导致对香味化合物的过敏性接触性皮炎增加。许多香料化合物易于自氧化，形成氢过氧化物作为其主要氧化产物。已知氢过氧化物是强过敏原并形成特异性免疫原性复合物。然而，免疫原性复合物的形成机制在很大程度上是未知的。我们研究了（5 R）-5-异丙烯基-2-甲基-2-环己烯-1-过氧化氢（Lim-2-OOH）在保护的半胱氨酸（NAc-Cys-OMe）或谷胱甘肽（GSH）存在下与5，10，15，20-四苯基-21H，23H-卟吩氯化铁（Fe（III）TPPCl）反应生成加合物的机理。分离的加合物来源于NAc-Cys-OMe的硫醇基团在香芹酮的碳-碳双键上的加成。此外，NAc-Cys-OMe和香芹醇之间以及GSH和香芹酮之间的加合物已经被鉴定。这些加合物的形成最有可能通过自由基硫醇-烯机制进行。在半胱氨酸中加入萜烯部分，解释了免疫反应对结构不同的氢过氧化物的特异性。这些结果也解释了香芹酮和Lim-2-OOH之间缺乏交叉反应性。总之，我们建议，免疫原性复合物的烯烃氢过氧化物调用通过自由基硫醇烯机制形成。由于包含衍生自氢过氧化物的萜烯部分，这些络合物将对单独的烯属氢过氧化物具有特异性。
The widespread use of scented products causes an increase of allergic contact dermatitis to fragrance compounds in Western countries today. Many fragrance compounds are prone to autoxidation, forming hydroperoxides as their primary oxidation products. Hydroperoxides are known to be strong allergens and to form specific immunogenic complexes. However, the mechanisms for the formation of the immunogenic complexes are largely unknown. We have investigated this mechanism for (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH) by studying the formation of adducts in the reaction between this hydroperoxide and 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) in the presence of protected cysteine (NAc-Cys-OMe) or glutathione (GSH). Isolated adducts originate from the addition of the thiol group of NAc-Cys-OMe over the carbon-carbon double bonds of carvone. Furthermore, adducts between NAc-Cys-OMe and carveol as well as between GSH and carvone have been identified. The formation of these adducts most likely proceeds via the radical thiol-ene mechanism. The addition of a terpene moiety to cysteine offers an explanation of the specificity of the immune response to structurally different hydroperoxides. These results also explain the lack of cross-reactivity between carvone and Lim-2-OOH. In conclusion, we propose that immunogenic complexes of olefinic hydroperoxides call be formed via the radical thiol-ene mechanism. These complexes will be specific for the individual olefinic hydroperoxides due to the inclusion of a terpene moiety derived from the hydroperoxide.