Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin.
METHODS
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.
Dermatology Service, Veterans Affairs Medical Center, San Francisco, CA 94121.
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D000096:Acetone / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D002518:Ceramides / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000648:ultrastructure; D012879:Skin Physiological Phenomena; D014870:Water Loss, Insensible / Q000187:drug effects
D002518:Ceramides; D005227:Fatty Acids; D008055:Lipids; D000096:Acetone; D002784:Cholesterol