Historical Perspectives

Many published accounts of the composition of lipids from human stratum corneum have been complicated by the almost inevitable presence of sebaceous lipids as well as exogenous contaminants. When stratum corneum samples are obtained from excised skin, there is almost always massive contamination with subcutaneous triglycerides as well as fatty acids derived from the subcutaneous fat. In addition, precautions must be taken to avoid contamination with environmental contaminants such as alkanes and cosmetic components. As a result of these complications, much work has been done with pig skin as a model [1-6].

Young pigs, if properly housed and tended, can be kept clean, and the sebaceous glands are not active. By direct heat separation of epidermis from an intact carcass, it is possible to avoid subcutaneous fat. In terms of general structure, composition, and permeability barrier function, the pig appears to provide a good model for the human. An alternative approach is to use the contents of epidermal cysts [7,8]. This material represents exfoliated stratum corneum lipid that is free of sebaceous and environmental contaminants. If the contents are carefully expressed from the capsule, a contaminant-free sample of stratum corneum lipid can be obtained. Cholesterol sulfate is partially hydrolyzed during the desquamation process; however, this is only a minor stratum corneum component. In either the pig or cyst model, the major lipid components are ceramides, cholesterol, and fatty acids, which represent approximately 45, 27, and 12% of the total lipid, respectively

[9]. Other minor components include cholesterol sulfate and cholesterol esters. The fatty acids in either model are predominantly straight-chain saturated species ranging from either 14 (cyst) or 16 (pig) carbons through 28 carbons in length with the 22 and 24 carbon species being the most abundant. The main focus in the rest of this chapter will be on the stratum corneum ceramides.

The first analysis of stratum corneum lipids was performed in 1932 by Kooyman

[10], who showed a dramatic reduction in the proportion of phospholipid in stratum corneum compared with the inner portion of the epidermis. Subsequently, Long [11], using

the very thick epidermis from cow snout as a model, analyzed lipids from horizontal slices of epithelial tissue. He observed a gradual accumulation of cholesterol and fatty acids in progressing from the basal region toward the surface. Phospholipids initially accumulated, but were degraded as the stratum corneum was approached. In 1965, Nicolaides [12] identified ceramides as a polar lipid component of stratum corneum. This fact was included in a footnote and was largely ignored until the pioneering work of Gray and Yardley in the mid to late 1970s [1,2,13,14]. Among other things, these investigators showed that the ceramides are structurally heterogeneous and contain normal fatty acids, a-hydroxyacids, sphingosines, and phytosphingosines as components. However, individual ceramide types were not well resolved and no definitive structures could be proposed. The first attempt to isolate individual ceramide types and to determine the identities of the individual fatty acid and long-chain base components was conducted in 1979 using neonatal mouse epidermis as a source of lipids [15]. Eight putative ceramide fractions were isolated, and six of these were analyzed. The remaining two were too minor for any analysis. Unfortunately, only normal fatty acids, sphingosines, and dihydrosphingosines were reported for each fraction analyzed. This suggests extensive cross-contamination sufficient to preclude recognition of the actual structural diversity. In 1983, the detailed structures of the ceramides from porcine epidermis were published [3]. Six structurally different types of ceramides were identified, and these included sphingosines, dihydrosphingosines, and phytosphin-gosines as the base components; normal, a-hydroxyacids, and m-hydroxyacids as the amide-linked fatty acids; and one ceramide type included an ester-linked fatty acid. Subsequently, it was shown that the same ceramide structural types are present in human stratum corneum, although the proportions are somewhat different [8,15]. More recently it has been shown that in addition to the standard phytosphingosine present in porcine ceramides, the human ceramides also include a variant phytosphingosine, 6-hydroxysphingosine [16].

In 1987 it was discovered that porcine epidermal stratum corneum contains significant levels of covalently bound lipid, the major component of which is an m-hydroxycera-mide [4]. Small amounts of saturated fatty acid and m-hydroxyacid are also present. A similar situation was shown for human stratum corneum; however, in this case there was a second hydroxyceramide that was shown to contain a variant phytosphingosine [17]. This subsequently proved to be 6-hydroxysphingosine [16]. The free and covalently bound ceramides are discussed in detail in the following section.

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