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A more recent version of this article appeared on December 1, 2007

Papers In Press, published online ahead of print September 13, 2007
J. Lipid Res., doi:10.1194/jlr.R700013-JLR200
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Submitted on June 18, 2007
Revised on September 10, 2007
Accepted on September 11, 2007

The role of epidermal lipids in cutaneous permeability barrier homeostasis

Kenneth R. Feingold

Medicine, VA Medical Center, San Francisco, CA 94121

Corresponding Author: kenneth.feingold{at}ucsf.edu

The permeability barrier is required for terrestrial life and is localized to the stratum corneum where extracellular lipid membranes inhibit water movement. The lipids that comprise the extracellular matrix have a unique composition and are 50% ceramides, 25% cholesterol, and 15% free fatty acids. Essential fatty acid deficiency results in abnormalities in stratum corneum structure function. The lipids are delivered to the extracellular space by the secretion of lamellar bodies which contain phospholipids, glucosylceramides, sphingomyelin, cholesterol, and enzymes. In the extracellular space the lamellar body lipids are metabolized by enzymes to the lipids that form the lamellar membranes. The lipids contained in the lamellar bodies are derived from both epidermal lipid synthesis and extracutaneous sources. Inhibition of cholesterol, fatty acid, ceramide, or glucosylceramide synthesis adversely affects lamellar body formation thereby impairing barrier homeostasis. Studies have further shown that the elongation and desaturation of fatty acids is also required for barrier homeostasis. The mechanisms that mediate the uptake of extracutaneous lipids by the epidermis are unknown but keratinocytes express LDL and SR-B1 receptors, fatty acid transport proteins, and CD36. Topical application of physiologic lipids can improve permeability barrier homeostasis and have been useful in the treatment of cutaneous disorders.


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