Skin Lipids for Barrier Function

Abstract

INTRODUCTION A primary function of the skin of terrestrial vertebrates is the provision of a water-tight barrier (1). Without this excellent barrier, life on dry land could not have evolved. In 1944, Windsor and Burch published the first evidence implicating the stratum corneum as the location of the permeability barrier (2). They monitored water loss through the abdominal skin of anesthetized surgery patients as they abraded the skin by rubbing with fine sandpaper. They found that there was a major increase in water loss just as the last of the stratum corneum was breached. In 1953, Blank did a more refined variation of this experiment in which the stratum corneum was progressively removed by stripping with cellophane tape (3). This clearly showed that the barrier resided within the stratum corneum. At about this same time, experiments implicated lipids in the barrier function of human skin (4). Extraction of skin with organic solvents that removed lipids resulted in large increases in permeability. At this time little was known about the nature of the lipids in epidermis or in stratum corneum. Kooyman had shown that the viable portion of the epidermis contained phospholipids and that these lipids were largely replaced by less polar lipids in the stratum corneum (5). Subsequently, long examined lipids in slices cut from cow snout (6). He showed that phospholipids initially increased and then decreased when moving from the inner epidermis to the outer stratum corneum. At the same time, fatty acids, cholesterol, and some relatively nonpolar unidentified lipids increased. The unidentified material in this report had, in fact, been identified as ceramide several years earlier by Nicolaides (7). However, this finding was published as a footnote added in proof to an article in a very specialized journal. The picture that emerges from these early studies is one in which the composition of the epidermal lipids alters with differentiation to produce a mixture consisting largely of ceramides, cholesterol, and fatty acids in the stratum corneum. This compartment provides the barrier function of the skin.