Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function.
Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function.
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DOI：
10.1038/jid.2003.11
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发表时间：
2003-06
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通讯作者：
M. Behne;N. Barry;K. M. Hanson;I. Aronchik;Robert W. Clegg;E. Gratton;K. Feingold;W. Holleran;P. Elias;T. Mauro
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文献类型：
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作者：
M. Behne;N. Barry;K. M. Hanson;I. Aronchik;Robert W. Clegg;E. Gratton;K. Feingold;W. Holleran;P. Elias;T. Mauro
虽然基础通透性屏障功能在出生时就已确立，但感染、皮炎和有毒物质经皮吸收的风险较高，可能表明通透性屏障在新生儿早期就成熟不完全。由于成人角质层(SC)的酸化是正常通透性屏障动态平衡所必需的，而脂质加工是通过酸性pH依赖的酶进行的，我们假设，伴随着较低酸性的表面pH，新生儿SC将显示出不完全屏障形成的迹象。荧光寿命成像显示，新生大鼠在出生后第3天，SC酸化开始变得明显，在SC颗粒层(SG)界面的细胞外“微域”，已知发生了对pH敏感的脂质处理。这种局部酸化与分泌的板层小体内容物被有效地处理成成熟的细胞外板层双层有关。由于关键的酸化机制NHE1在出生前表达最多，并在出生后第一周逐渐下降，出生时SC的亚酸化不能归因于NHE1的表达不足，而可能反映NHE1活性的降低。脂类加工的关键酶β-葡萄糖脑苷酶(β-GlcCer‘ase)的表达与NHE1相似，但缺乏β-GlcCer’ase蛋白作为有效脂加工的限速酶。这些结果定义了一种出生后发育，包括下部SC的初始酸化和随后的向外发展，并伴随着成熟的细胞外板层膜的形成。因此，完整的屏障能力似乎需要在出生后立即从SC/SG界面向外向皮肤表面延伸微域中的酸化。
Although basal permeability barrier function is established at birth, the higher risk for infections, dermatitis, and percutaneous absorption of toxic agents may indicate incomplete permeability barrier maturation in the early neonatal period. Since stratum corneum (SC) acidification in adults is required for normal permeability barrier homeostasis, and lipid processing occurs via acidic pH dependent enzymes, we hypothesized that, in parallel with the less acidic surface pH, newborn SC would exhibit signs of incomplete barrier formation. Fluorescence lifetime imaging reveals that neonatal rat SC acidification first becomes evident by postnatal day 3, in extracellular “microdomains” at the SC- stratum granulosum (SG) interface, where pH-sensitive lipid processing is known to occur. This localized acidification correlated temporally with efficient processing of secreted lamellar body contents to mature extracellular lamellar bilayers. Since expression of the key acidifying mechanism NHE1 is maximal just prior to birth, and gradually declines over the first postnatal week, subop-timal SC acidification at birth cannot be attributed to insufficient NHE1 expression, but could instead reflect reduced NHE1 activity. Expression of the key lipid processing enzyme, β-glucocerebrosidase (β-GlcCer’ase), develops similar to NHE1, excluding a lack of β-GlcCer’ase protein as rate limiting for efficient lipid processing. These results define a postnatal development consisting of initial acidification in the lower SC followed by outward progression, which is accompanied by formation of mature extracellular lamellar membranes. Thus, full barrier competence appears to require the extension of acidification in microdomains from the SC/SG interface outward toward the skin surface in the immediate postnatal period.