ABSTRACT

UNDERSTANDING THE SKIN BARRIER FUNCTION The stratum corneum (SC), the outer permeability barrier of the skin, is continuously exposed to physical and chemical agents from the environment. As a highly specialized structure, it is essentially impermeable to water, except for a small but vital flux serving to maintain its hydration and flexibility (1). As discussed in Chapters 7 and 24 of this volume, the SC is a very resilient tissue. The physical barrier to permeation through the skin, located in the SC, is primarily a function of the long-chain lamellar lipids that fill the intercellular space between the corneocytes. To account for such barrier properties and for the hydrophilic and hydrophobic pathways through the skin barrier, an alternative model to the “brick-and-mortar” model, the domain mosaic model, has been proposed (2). This model envisages the barrier lipids as existing predominantly in crystalline domains, surrounded by grain borders of lipids in a liquid crystalline state. The latter provide an effective barrier that allows a small, but controlled, water loss through the liquid interdomains, which is sufficient to keep the SC keratin hydrated. Perturbation in the barrier due to the use of organic solvents, detergents, or mechanical abrogation leads to an altered water flux and initiates a cascade of events within the underlying epidermis to promote barrier recovery. The principal response to minor repeated or severe barrier disruption comprises a temporary increase in the biosynthesis of all major lipid species in the epidermis, enhanced cytokine production, inflammatory events involving the deeper layers of the skin and the endothelium, epidermal hyperplasia, and abnormal keratinization.