EXOGENOUS LIPIDS INFLUENCE PERMEABILITY BARRIER RECOVERY IN ACETONE-TREATED MURINE SKIN

EXOGENOUS LIPIDS INFLUENCE PERMEABILITY BARRIER RECOVERY IN ACETONE-TREATED MURINE SKIN
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DOI:
10.1001/archderm.129.6.728
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发表时间:
1993-06-01
影响因子:
--
通讯作者:
ELIAS, PM
ELIAS, PM
中科院分区:
其他
文献类型:
--
作者:
MAN, MQ;FEINGOLD, KR;ELIAS, PM

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背景和设计。当用丙酮干扰表皮渗透屏障时,经皮水分损失在24小时内恢复正常,同时角质层脂质重现,来源于分泌的板层体和加速的脂质合成。先前的研究已经证明了屏障稳态对胆固醇、脂肪酸和神经酰胺合成的单独需求,但是屏障功能对这些脂质单独或一起的需求尚不清楚。因此,我们将这些脂质单独或以各种混合物应用于丙酮处理的无毛小鼠皮肤并评估屏障恢复。单独的神经酰胺和脂肪酸,以及它们的复合衍生物(胆固醇酯和胆固醇苷),以及脂肪酸加神经酰胺、胆固醇加脂肪酸或胆固醇加神经酰胺的双组分混合物延迟屏障恢复。 相反,神经酰胺、脂肪酸和胆固醇的完全混合物允许正常的屏障恢复。此外,荧光标记的胆固醇,脂肪酸和神经酰胺迅速穿过角质层吸收到表皮有核层。最后,不完全的,但不完全的混合物产生异常板层体,导致异常角质层细胞间膜双层。(1)局部应用单个脂质或脂质的不完全混合物干扰屏障恢复,而胆固醇、脂肪酸和神经酰胺的完全混合物允许正常的屏障修复;和(2)局部脂质的不完全混合物似乎抑制板层体水平的屏障恢复,导致角质层中的异常细胞间膜结构,当提供完全脂质混合物时不会发生的异常。
Background and Design.-When the epidermal permeability barrier is perturbed with acetone, transcutaneous water loss returns to normal over 24 hours in parallel with the reappearance of stratum corneum lipids, derived from secreted lamellar bodies and accelerated lipid synthesis. Prior studies have demonstrated a separate requirement for cholesterol, fatty acid, and ceramide synthesis for barrier homeostasis, but the requirement for these lipids individually or together for barrier function is not known. We therefore applied these lipids alone or in various mixtures to acetone-treated hairless mouse skin and assessed barrier recovery.Results.-Ceramide and fatty acid alone, and their complex derivatives (cholesterol esters and cerebrosides), and two-component mixtures of fatty acid plus ceramide, cholesterol plus fatty acid, or cholesterol plus ceramide delayed barrier recovery. In contrast, complete mixtures of ceramide, fatty acid, and cholesterol allowed normal barrier recovery. Moreover, fluorescent-labeled cholesterol, fatty acid, and ceramide rapidly traversed the stratum corneum with uptake into the epidermal nucleated layers. Finally, incomplete, but not complete mixtures produce abnormal lamellar bodies, leading to abnormal stratum corneum intercellular membrane bilayers.Conclusions.-(1) Topical applications of individual lipids or incomplete mixtures of lipids interfere with barrier recovery, while complete mixtures of cholesterol, fatty acid, and ceramide allow normal barrier repair; and (2) incomplete mixtures of topical lipids appear to inhibit barrier recovery at the level of the lamellar body resulting in abnormal intercellular membrane structures in the stratum corneum, abnormalities that do not occur when a complete lipid mixture is provided.