Epidermal Lipids and the Intercellular Pathway

Abstract

The epidermis is the keratinizing epithelium covering the skin. The basal layer of the epidermis includes the replicative cells as well as cells that serve to anchor the epidermis to the underlying tissue. Immediately above the basal layer are the spinous cells, characterized by their numerous desmosomal connections. Above this are the multiple layers of granular cells, characterized by their proteinaceous keratohyalin granules. The outermost portion of the epidermis is the stratum corneum, which consists of flattened, keratin cells embedded in a lipid matrix. In the cells of the stratum corneum, the cell plasma membrane, present in the lower strata, has become replaced by a thick band of cross-linked protein with a covalently bound layer of lipid on the outer surface. As cells differentiate in the epidermis, they accumulate keratins and other proteins as well as lipids as they move out toward the skin surface. Much of the lipid that accumulates with increasing differentiation is packaged into small organelles known as lamellar granules. At the boundary between the uppermost granular cells and the bottom of the stratum corneum, lipids are extruded from the lamellar granules into the intercellular space. As these lipids pass into the stratum corneum, they are acted upon by a battery of hydrolytic enzymes to produce a mixture of ceramides, cholesterol, and fatty acids that fill the intercellular spaces of the stratum corneum. Under conditions of passive diffusion, molecules penetrating into the skin pass through the intercellular spaces of the stratum corneum. The intercellular lipids provide the primary permeability barrier of the skin.