title: Exogenous nonphysiologic vs physiologic lipids. Divergent mechanisms for correction of permeability barrier dysfunction.
abstract: METHODS
  Although barrier function requires cholesterol, free fatty acids, and ceramides, applications of one or two of these lipids to damaged skin impedes barrier recovery, while equimolar mixtures allow normal recovery. Both incomplete and complete mixtures appear to be internalized within the epidermal nucleated layers, followed by the secretion of abnormal vs normal lamellar body contents, respectively. We compared the ability of complete physiologic lipid mixtures vs a nonmetabolized hydrophobic lipid, petrolatum, to repair the barrier and the requirement for intracellular processing of these lipids within the epidermis.
  
  
  RESULTS
  Neat petrolatum, which remains restricted to the stratum corneum, produces more rapid improvement in barrier function than the solvent-dispersed physiologic lipids, and its effects are not altered by coapplication of either monensin or brefeldin A (both from Sigma Chemical Co, St Louis, Mo), known inhibitors of exocytosis and organellogenesis, respectively. In contrast, the physiologic lipids enter the nucleated layers in substantial amounts and require longer to produce barrier recovery. Whereas monensin blocks their ability to facilitate barrier recovery, the physiologic lipids overcome brefeldin A-induced delays in barrier recovery, bypassing the subcellular site of brefeldin A blockade, normalizing both lamellar body contents and intercellular bilayers.
  
  
  CONCLUSIONS
  While petrolatum remains restricted to the stratum corneum, physiologic lipid mixtures influence barrier recovery after transport to subjacent, nucleated layers, followed by internalization, apparent transport to the distal Golgi apparatus, and incorporation into nascent lamellar bodies.
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, San Francisco, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mao-Qiang
authors.forename: B E
authors.initials: BE
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Wu-Pong
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000818:Animals; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D008055:Lipids / Q000493:pharmacokinetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008985:Monensin / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010577:Petrolatum / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D003517:Cyclopentanes; D008055:Lipids; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D010577:Petrolatum; D008985:Monensin