Deficiency of epidermal protein-bound ω-hydroxyceramides in atopic dermatitis
Deficiency of epidermal protein-bound ω-hydroxyceramides in atopic dermatitis
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DOI：
10.1046/j.1523-1747.2002.01833.x
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发表时间：
2002-07-01
影响因子：
6.5
通讯作者：
Sandhoff, K
中科院分区：
文献类型：
--
作者：
Macheleidt, O;Kaiser, HW;Sandhoff, K
特应性皮炎是一种病因不明的常见皮肤病，其渗透屏障功能受损。为了了解更多关于病变皮肤的分子病理学，我们分析了特应性皮炎受试者表皮中游离可提取物和蛋白结合屏障脂质的水平。健康表皮中蛋白质结合的ω-羟基神经酰胺的量占总蛋白质结合的脂质的46-53重量%，而该百分比在受试者的非病变区域中降低至23-28重量%，甚至在受影响的特应性皮肤区域中降低至10-25重量%。此外，与健康对照相比，在特应性皮炎受试者的受影响区域中具有超过24个碳原子的游离可提取极长链脂肪酸的部分量降低至25重量%，在非病变区域中降低至40重量%。这种“烃链长度不足”的屏障脂质在特应性皮肤支持的代谢标记研究与[（14）C]-丝氨酸在培养的表皮。与健康对照受试者相比，特应性受试者的受影响皮肤区域中游离葡萄糖神经酰胺和游离神经酰胺的生物合成显著降低。特别受影响的是神经酰胺4的从头合成（即，神经酰胺EOH，由亚油酸酯化的极长链N-酰基ω-羟基脂肪酸和作为鞘氨醇碱的6-羟基鞘氨醇组成）和神经酰胺3（神经酰胺NP，由非羟基N-酰基脂肪酸和植物鞘氨醇组成）。总之，这项研究表明，特应性皮炎的病变表皮的主要屏障脂质成分有相当大的缺陷，这可能有助于严重受损的渗透性屏障。
Atopic dermatitis is a common skin disease of unknown etiology with an impaired permeability barrier function. To learn more about the molecular pathology in lesional skin, we analyzed levels of free extractable as well as protein-bound barrier lipids in the epidermis of atopic dermatitis subjects. The amount of protein-bound omega-hydroxyceramides in healthy epidermis comprised 46-53 wt% of total protein-bound lipids, whereas this percentage was decreased to 23-28 wt% in nonlesional areas and even down to 10-25 wt% in affected atopic skin areas of the subjects. Furthermore, the partial amount of free extractable very long chain fatty acids with more than 24 carbon atoms was reduced in affected regions down to 25 wt% and in nonlesional regions of the atopic dermatitis subjects down to 40 wt% compared to healthy controls. This "hydrocarbon chain length deficiency" regarding the barrier lipids in atopic skin was supported by metabolic labeling studies with [(14) C]-serine in cultured epidermis. The biosynthesis of free glucosylceramides and free ceramides was remarkably decreased in affected skin areas of the atopic subjects compared to healthy control subjects. Especially affected were the de novo syntheses of ceramide 4 (i.e., ceramide EOH, consisting of a very long chain N-acyl omega-hydroxy fatty acid esterified with linoleic acid and 6-hydroxysphingosine as sphingoid base) and ceramide 3 (ceramide NP, consisting of a nonhydroxy N-acyl fatty acid and phytosphingosine). In conclusion, this study revealed that the lesional epidermis in atopic dermatitis has considerable deficiencies within main barrier lipid components, which may contribute to the severely damaged permeability barrier.