EXOGENOUS NONPHYSIOLOGIC VS PHYSIOLOGICAL LIPIDS - DIVERGENT MECHANISMS FOR CORRECTION OF PERMEABILITY BARRIER DYSFUNCTION

Background and Design: 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 mixtu res allow normal recovery. Both incomplete and complete mixtures appea r to be internalized within the epidermal nucleated layers, followed b y the secretion of abnormal vs normal lamellar body contents, respecti vely. We compared the ability of complete physiologic lipid mixtures v s a nonmetabolized hydrophobic lipid, petrolatum, to repair the barrie r and the requirement for intracellular processing of these lipids wit hin the epidermis. Results: Neat petrolatum, which remains restricted to the stratum corneum, produces more rapid improvement in barrier fun ction than the solvent-dispersed physiologic lipids, and its effects a re not altered by coapplication of either monensin or brefeldin A (bot h from Sigma Chemical Co, St Louis, Mo), known inhibitors of exocytosi s and organellogenesis, respectively. In contrast, the physiologic lip ids enter the nucleated layers in substantial amounts and require long er to produce barrier recovery. Whereas monensin blocks their ability to facilitate barrier recovery, the physiologic lipids overcome brefel din A-induced delays in barrier recovery, bypassing the subcellular si te of brefeldin A blockade, normalizing both lamellar body contents an d intercellular bilayers. Conclusions: While petrolatum remains restri cted to the stratum corneum, physiologic lipid mixtures influence barr ier recovery after transport to subjacent, nucleated layers, followed by internalization, apparent transport to the distal Golgi apparatus, and incorporation into nascent lamellar bodies.