FOUNDING EDITORS DAVID KRITCHEVSKY RODOLFO PAOLETTI EDITORIAL ADVISORY BOARD G AlLHAUD R M BELL P LAGGNER I PASCHER G H ROTHBLAT FOUNDING EDITORS DAVID KRITCHEVSKY RODOLFO PAOLETTI EDITORIAL ADVISORY BOARD G AlLHAUD R M BELL P LAGGNER I PASCHER G H ROTHBLAT Advances in Lipid Research Volume 24 Skin Lipids Edited by PETER M ELIAS Department of Dermatology University of California, San Francisco San Francisco, California SERIES EDITORS RICHARD J HAVEL Cardiovascular Research Institute University of California, San Francisco San Francisco, California DONALD M SMALL Department of Biophysics Boston University Boston, Massachusetts ACADEMIC PRESS, INC ^ S Harcourt Brace Jovanovich, Publishers San Diego New York Boston London Sydney Tokyo Toronto This book is printed on acid-free paper @ Copyright © 1991 by ACADEMIC PRESS, INC All Rights Reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher Academic Press, Inc San Diego, California 92101 United Kingdom Edition published by Academic Press Limited 24-28 Oval Road, London NW1 7DX Library of Congress Catalog Number: 63-22330 International Standard Book Number: 0-12-024924-3 PRINTED IN THE UNITED STATES OF AMERICA 91 92 93 94 PREFACE This volume of Advances in Lipid Research is intended to provide a unique resource, with a comprehensive and current overview of the field of skin lipids Because of the acknowledged importance of epidermal lipids for cutaneous barrier function, the first three chapters address structural, biochemical, and metabolic aspects of the role of lipids in permeability barrier formation and maintenance In addition, Chapters Six and Seven describe the lipid biophysics of the intercellular lipid domains in the stratum corneum, and the regulation of percutaneous absorption by these domains, respectively Chapter Four describes the lipid content and metabolism of cultured keratinocytes, grown under standard immersed conditions and in various in vitro systems that attempt to produce an epidermal equivalent, including a competent barrier The remaining chapters cover a broad panoply of subjects not directly related to the epidermal barrier Chapter Eight describes the role of epidermal lipids in the pathogenesis of several disorders of cornification and the insights gained from these "experiments of nature" about the role of specific lipids in normal cohesion and desquamation Chapter Five discusses the important new field of lipid signaling mechanisms in the epidermis, focusing on the emerging potential role of sphingolipid metabolites in regulating epidermal proliferation and differentiation A discussion of eicosanoids is specifically not included, however, since this subject has been exhaustively covered in several recent reviews The ninth chapter provides a comprehensive description of the biochemistry of mammalian sebaceous gland lipids, including speculations about the function of some of these species in normal and diseased skin (e.g., acne) Chapter Ten compares the structure, function, and lipid biochemistry of integumental lipids from plants, invertebrates, and cold blooded vertebrates to warm-blooded (homeothermic) organisms Finally, Chapter Eleven reviews the explosion of new information about vitamin D and the skin, including new clinical, pathophysiological, and therapeutic applications Again, we have specifically chosen not to include chapters on the other major fat-soluble vitamin known to influence epidermal function (i.e., vitamin A), only because so many recent, exhaustive reviews of this subject are already available In summary, this volume not only provides abundant current and comprehensive information, but also each of the chapters represents a unique effort in the literature PETER M IX ELIAS ADVANCES IN LIPID RESEARCH, VOL 24 Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier PETER M ELIAS AND GOPINATHAN K MENON Dermatology Service Veterans Administration Medical Center San Francisco, California 94121 and Department of Dermatology University of California School of Medicine San Francisco, California 94143 I II III IV Introduction and Historical Perspective Stratum Corneum Two-Compartment Model Cellular Basis for Lipid-Protein Sequestration in the Stratum Corneum of Terrestrial Mammals Insights from Aves and Marine Mammals (Cetaceans) A Aves B Marine Mammals (Cetaceans) V Intercellular Membrane Structures in Mammalian Stratum Corneum VI Structural Alterations in Pathological Stratum Corneum VII Structural-Lipid Biochemical Correlates VIII Summary References I Introduction and Historical Perspective A pivotal point in terrestrial adaptation is prevention of desiccation and main tenance of internal water homeostasis Mammals have evolved an impressive array of adaptive responses for water conservation, among the most remarkable of which is the development of a cutaneous barrier to water loss The outermost integumentary tissue, the epidermis, maintains a reserve of germinal cell layers whose proliferation, stratification, and differentiation result in production of the outermost layer, the anucleate stratum corneum The loose "basketweave" pattern of the stratum corneum in typical histological preparations delayed appreciation of its responsibility for cutaneous barrier function Physical chemists were the first to show that the stratum corneum is extremely resilient, possessing the per meability properties of a homogeneous film (for review see Scheuplein and Blank, 1971) Later studies revealed the stratum corneum to be composed of in terlocking, vertical columns of foreshortened polyhedral cells, with thickened membrane envelopes (MacKenzie, 1969; Christophers, 1971; Menton and Eisen, 1971) More recent work has revealed the unique structural organization of this tissue into a two-compartment system (see below) Copyright © 1991 by Academic Press, Inc All rights of reproduction in any form reserved PETER M ELIAS AND GOPINATHAN K MENON The importance of stratum corneum lipids for barrier integrity has been appre ciated for several decades For example, the observation that topical applications of organic solvents produce profound alterations in barrier function is over 40 years old (for review see Scheuplein and Blank, 1971) More recently, the impor tance of bulk stratum corneum lipids for the barrier has been demonstrated by (1) the inverse relationship between the permeability of the stratum corneum to water and water-soluble molecules at different skin sites (e.g., abdomen versus palms and soles) and the lipid content of the first site (Elias et al., 1981a; Lampe et al., 1983a), (2) the observation that organic solvent-induced perturbations in barrier function occur in direct proportion to the quantities of lipid removed (Grubauer et al., 1989a), (3) the observation that stratum corneum lipid content is deficient or defective in pathological states that are accompanied by compromised barrier function, such as essential fatty acid deficiency (Elias and Brown, 1978), and, fi nally, (4) that replenishment of stratum corneum lipids, which follows removal by solvents or detergent, parallels the recovery of barrier function (Menon et al., 1985a; Grubauer et al, 1989b) II Stratum Corneum Two-Compartment Model More recently, the concept of the stratum corneum as merely a homogeneous film has been replaced by a model of the stratum corneum consisting of proteinenriched corneocytes embedded in a lipid-enriched, intercellular matrix (Fig 1) (Elias, 1983), i.e., a continuous lipid phase surrounding a discontinuous protein 1WO-