Gay C L, Guy R H, Golden G M, Mak V H, Francoeur M L
Central Research Division, Pfizer, Inc., Groton, Connecticut.
J Invest Dermatol. 1994 Aug;103(2):233-9. doi: 10.1111/1523-1747.ep12393214.
This study aims to characterize human stratum corneum (SC), focusing on those lipid transitions that occur at or below physiologically relevant temperatures. In the past, a lipid transition near 35 degrees C had been thought to be variable and a consequence of superficial sebaceous lipid contamination. However, analysis here indicates that it is widely present, and cannot be attributed to sebum production. We demonstrate that this transition represents a solid-to-fluid phase change for a discrete subset of SC lipids. The reversibility of this transition upon reheating, and its absence in extracted lipid samples imply that these lipids are not uniformly present throughout the SC, but would appear to be differentially distributed in response to terminal differentiation. Further, such an arrangement could involve a close association with other nonlipid (e.g., protein) components. Evidence for a new transition at approximately 55 degrees C is presented that suggests the loss of crystalline orthorhombic lattice structure. The existence of orthorhombic structure at physiologic temperature is reasoned to involve ceramides and/or free fatty acids. Localization of these lipids at the level of the corneocyte envelope supports a comprehensive picture of water transport across the SC, whereby diffusion occurs primarily via the intercellular lipids. This view, coupled with the hydration-induced changes in lipid disorder observed here provides additional insight into the mechanism by which skin occlusion increases permeability. Summarily, these results i) emphasize the inherent danger of over-interpreting experiments with isolated SC lipids, ii) emphasize the potential advantage(s) of employing several biophysical techniques to study SC structure, and iii) indicate that a full characterization of lipid phase behavior is requisite to our eventual understanding of SC structure and permeability function, particularly those phase transitions that occur near or at normal skin temperature.
本研究旨在表征人体角质层(SC),重点关注在生理相关温度或以下发生的脂质转变。过去,人们认为接近35摄氏度的脂质转变是可变的,是浅表皮脂腺脂质污染的结果。然而,此处的分析表明它广泛存在,且不能归因于皮脂分泌。我们证明这种转变代表了SC脂质离散子集的固-液相变。这种转变在重新加热时的可逆性,以及在提取的脂质样品中不存在这种转变,意味着这些脂质在整个SC中并非均匀存在,而是似乎根据终末分化呈差异分布。此外,这样的排列可能涉及与其他非脂质(如蛋白质)成分的紧密结合。本文提出了在大约55摄氏度时新转变的证据,这表明正交晶系晶格结构的丧失。据推测,生理温度下正交晶系结构的存在涉及神经酰胺和/或游离脂肪酸。这些脂质在角质形成细胞包膜水平的定位支持了关于水通过SC运输的全面图景,即扩散主要通过细胞间脂质发生。这种观点,再加上此处观察到的水合作用引起的脂质无序变化,为皮肤闭塞增加通透性的机制提供了额外的见解。总之,这些结果:i)强调了过度解读分离的SC脂质实验的内在风险;ii)强调了采用多种生物物理技术研究SC结构的潜在优势;iii)表明脂质相行为的全面表征对于我们最终理解SC结构和通透性功能是必要的,特别是那些在正常皮肤温度附近或在正常皮肤温度时发生的相变。