Comeocytes

The skin barrier properties and effect of hand hygiene practices are known to be important in protecting the body. The average adult has a skin area of about 1.75 m2. The superficial part of the skin, the epidermis, has five layers. The stratum corneum, the outermost layer, is composed of flattened dead cells (comeocytes or squames) attached to each other to form a tough, homy layer of keratin mixed with several lipids, which help maintain the hydration, pliability, and barrier effectiveness of the skin. This part of skin has been compared to a wall of bricks (comeocytes) and mortar (lipids) and serves as the primary protective barrier. Approximately 15 layers make up the stratum corneum, which is completely replaced every 2 weeks a new layer is formed almost daily. From healthy skin, approximately 107 particles are disseminated into the air each day, and 10% of these skin squames contain viable bacteria. This is a source of major dirt inside the house and contributes to many interactions. 

The most superficial layer of skin is the stratum comeum (SC), which consists of terminally differentiated keratinocytes (comeocytes) that originate from actively proliferating keratinocytes in lower epidermis (basale, spinosum, and granulosum cells), and contain a lamellar lipid layer secreted from lamellar bodies (Fig. 7a). Flydration of the SC is an important determinant of skin appearance and physical properties, and depends on a number of factors including the external humidity, and its structure, lipid/protein composition, barrier properties, and concentration of water-retaining osmolytes (natural moisturizing factors, NMFs) including free amino acids, ions, and other small solutes. 

Swartzendruber, D.C., et al. 1987. Evidence that the comeocyte has a chemically bound lipid envelope. J Invest Dermatol 88 709. 

FIGURE 12.1 Penetration enhancer activity, (a) Action at intercellular lipids. Some of the ways by which penetration enhancers attack and modify the well-organized intercellular lipid domain of the stratum comeum. (b) Action at desmosomes and protein structures. Such dramatic disruption by enhancers (particularly potent solvents) as they split the stratum corneum into additional squames and individual cells would be clinically unacceptable, (c) Action within comeocytes. Swelling, further keratin denaturation and vacuolation within individual horny layer cells would not be so drastic but would usually be cosmetically challenging (see Menon and Lee [69] for further details). (Reproduced from Barry, B.W., Nat. Biotechnol. 22, 165, 2004. With permission.)... 

The barrier properties of human skin have long been an area of multidisciplinary research. Skin is one of the most difficult biological barriers to penetrate and traverse, primarily due to the presence of the stratum corneum. The stratum cor-neum is composed of comeocytes laid in a brick-and-mortar arrangement with layers of lipid. The corneocytes are partially dehydrated, anuclear, metabolically active cells completely filled with bundles of keratin with a thick and insoluble envelope replacing the cell membrane [29]. The primary lipids in the stratum corneum are ceramides, free sterols, free fatty acids and triglycerides [30], which form lamellar lipid sheets between the corneocytes. These unique structural features of the stratum comeum provide an excellent barrier to the penetration of most molecules, particularly large, hydrophilic molecules such as ASOs. 

Traditionally, components of the NMF are measured following extraction of comeocytes recovered from superficial tape-strippings, or from direct extraction of the skin surface by attaching open-ended chambers to the skin and eluting with small volumes of aqueous buffers or dilute surfactant solutions. By analysing sequential tape strips recovered from the same site profiles of how NMF levels change with depth can be constructed. These profiles indicate that the levels of NMF decline markedly toward the surface of the skin. This is typical of normal skin exposed to routine soap washing where much of the readily soluble NMF is washed out from the superficial SC.83... 

Dry skin is further characterized by structural changes in comeocyte envelope (CE) as a result of reduced transglutaminase activity. The enzyme is responsible for the transformation of a soft or fragile envelope into a rigid one. Fragile corneocyte envelopes predominate in dry skin.9... 

White, S.H., Mirejovsky, D., and King, G.I., Structure of lamellar domains and comeocyte envelopes of murine stratum corneum an X-ray diffraction study, Biochemistry, 27, 3725, 1988. 

FIGURE 28.7 Neat SEFA site from a 42-year-old male, (a) Comeocytes are closely apposed, with well-formed lamellae at the corneocyte surface. Between the lamellae is a relatively uniform layer of an amorphous material. This pattern is referred to as the SEFA look. (b) Occasional multiple Landmann units are present in the intercellular space. The length of the double Landmann units is always relatively short. Bar = 100 nm. 

The stratum comeum is usefully thought of as a brick wall , with the fully differentiated comeocytes comprising the bricks , embedded in the mortar created by the intercellular lipids. A layer of lipid covalently bound to the comified envelope of the comeocyte contributes to this exquisite organization. The intercellular lipids of the stratum comeum include no phosphohpids, comprising an approximately equimolar mixture of ceramides, cholesterol and free fatty acids. These non-polar and somewhat rigid components of the stratum comeum s cement play a critical role in barrier function. On average, there are about 20 cell layers in the stratum comeum, each of which is about 0.5 fim in thickness. Yet, the architecture of the membrane is such that this very thin structure limits, under normal conditions, the passive loss of water across the entire skin surface to only about 250 mL per day, a volume easily replaced in order to maintain homeostasis. 

SECM, was decreased by 8%, 23%, and 65% (from pretreated iontophoretic flux values) for 10-, 20-, and 30-minute pretreatment with SDS, respectively. It was concluded that the penetration enhancement effect of SDS alters the nonporous stmctures of the skin (i.e., keratin-filled comeocytes, intercellular lipid matrix). 

Figure 5 Murine stratum comeum normal full thickness. Powder diffraction patterns obtained from mouse SC at 25°C. The upper figure shows the small-angle lamellar pattern produced by the intercellular lipid domains, with a repeat period of 131 2 A. The lower figure shows the wide-angle pattern produced by the lipid alkyl chains and the comeocyte envelope. See text. (Data from White et al., 1988.)...

While a temperature-dependent IR spectrum allows one to examine specific elements of a transition, a DSC thermogram enables the visualization of transitions in their entirety and the calculation of associated thermodynamic parameters. The IR and DSC thermal profiles for identically treated samples of hydrated porcine SC are shown in Fig. 3. The results of a series of thermograms for intact, delipidized, fractionated, and reheated SC as well as extracted lipids suggest that these three major transitions near 60,70, and 95°C in intact SC are due to intercellular lipid, a lipid-protein complex associated with the comeocyte membrane, and intracellular keratin, respectively. Evidence supporting these deductions is elegantly presented by Golden et al. [33]. More recently, the presence of a subzero lipid transition at -9°C has also been reported [34]. 

Challenges for the use of biophysical techniques remain, however, not the least of which is whether they can be developed to unravel the structural heterogeneity of the SC. To what extent will it be possible to define the different lipid domains within the intercellular spaces and at the comeocyte... 

Abraham, W. and Downing, D. T. (1990). Interaction between comeocytes and stratum coraeum lipid liposomes in vitro. Biochim. Biophys. Acta 1021 119. 

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