Stratum corneum keratinocytes

Basket weave or compact stratum corneum, acanthosis and/or atrophy, keratinocyte atypia, flattened rete ridges... 

The skin consists of two main compartments, the epidermis, a stratified squamous epithelium, and the underlying dermis, a richly vascularized tissue embedded in a connective tissue matrix (Fig. 41.1). The epidermis consists of multiple layers of keratinocytes, which differentiate into the outermost layer, the stratum corneum. This layer contains the hydrophilic structural... 

Papilloma. A benign epithelial neoplasm producing finger-like or verrucous projections from the epithelial surface. Parakeratosis. Persistence of the nuclei of the keratinocytes into the stratum corneum (horny layer) of the skin. Parakeratosis is normal in the epithelium of true mucous membrane of the mouth and vagina. Parkinson s disease. Neurological disorder characterized by hypokinesia, tremor, and muscular rigidity. 

FIGURE 2.2 A diagram of human skin. Epidermal thickness depends upon body site being thickest on the palms and soles (-1500 pm) and thinnest around the eyes (-10 pm). The stratum corneum is the only layer composed of anucleated, terminally differentiated kerati-nocyte cells called corneocytes. All other epidermal layers contain nucleated keratinocytes. The dermis is composed primarily of the structural proteins collagen and elastin. 

The stratum granulosum is the most superficial cell layer of the viable epidermis and contains highly differentiated keratinocytes. The lamellar bodies, which have been formed in the stratum spinosum, migrate to the apical periphery of the uppermost granular cells and eventually fuse with the membrane of the keratinocyte. Via exocytosis their content is extruded into the intercellular spaces at the stratum granulosum-stratum corneum interface. The lipids derived from the lamellar bodies are essential for the formation of the stratum corneum barrier. 

Madison, K.C., et al. 1989. Murine keratinocyte cultures grown at the air/medium interface synthesize stratum corneum lipids and recycle linoleate during differentiation. J Invest Dermatol 93 10. 

Hofland, H.E., et al. 1991. Interactions of non-ionic surfactant vesicles with cultured keratinocytes and human skin in vitro A survey of toxicological aspects and ultrastructural changes in stratum corneum. J Control Release 16 155. 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

Fig. 12.3. Epidermal measurements, mitotic figures, and apoptotic keratinocytes in a chronic proliferative dermatitis mutant (Sharplncpdm/Sharplncpdm) mouse. Routine hematoxylin- and eosin-stained paraffin histologic sections can be used to determine proliferation rates based on mitotic index (number of mitotic figures, circled in the figure, in the stratum basale per 1000 cells) or the presence and numbers of apoptotic epidermal keratinocytes (dotted arrows) when present. Epidermal thickness can be measured at high dry magnification (40x) to include the malpigian, living cell, layer (M), the stratum corneum thickness (SC), or the full thickness of the epidermis (M+SC).

This chapter will deal with the stratum corneum barrier with a special focus on structure-function relationships. For this reason our approach has been to describe some details of the epidermal physiology that have a bearing on upholding the barrier function. We see it as important that skin barrier function is regarded as part of the dynamic processes of cellular transformation during the differentiation of epidermal keratinocytes, hence dependent on the status of the skin. 

Haftek, M., Serre, G., and Thivolet, J., Immunochemical evidence for a possible role of cross-linked keratinocyte envelopes in stratum corneum cohesion, J. Histochem. Cytochem., 39, 1531, 1991. 

Feingold and his coworkers demonstrated an important role of nuclear hormone receptor on epidermal differentiation and stratum corneum barrier formation. Activation ofPPARa Peroxisome proliferator-activated receptor a by farnesol also stimulated the differentiation of epidermal keratinocytes.42 Cornified envelope formation, involcrin, and transglutaminase protein, and mRNA levels were also increased by the activation of PPARo . Interestingly, the inflammatory response was also inhibited by the treatment.43 They also showed that topical application of PPARo activators accelerated the barrier recovery after tape stripping or acetone treatment and prevented the epidermal hyperplasia induced by repeated barrier disruption.42 Regulation of the nuclear hormone receptor would open a new possibility for improvement of the cutaneous barrier. 

Psoriasis is a chronic disease with hyperproliferation of the epidermis and inflammatory reactions of the dermis and epidermis. Psoriasis is characterized by an elevated turnover rate of keratinocytes. The duration of the cell cycle is shortened. Inflammation is characterized by the release of cytokines and an expression of CD4+ cells in psoriatic lesions of affected patients. Scaling marks the clinical feature associated with hyperkeratosis, pruritus, inflammation, and stratum corneum dryness. 

Dithranol in combination with urea is widely used in psoriasis to improve the clinical efficacy, to minimize the dithranol concentration, to achieve the desired effect, to shorten the contact, to get a better hydration of the stratum corneum, and to decrease the proliferation rate of the keratinocytes. Gabard and Bieli showed an increased keratolytical effect of salicylic acid by adding 10% urea.54 Hagemann and Proksch55 showed in 10 patients with psoriasis under a 2-week treatment with a 10% urea ointment increased stratum corneum hydration, a small decrease in TEWL, a reduction in epidermal thickness (-29%), and a decreased epidermal proliferation (-51%). The altered expression of involucrin and cytokeratins as marker for epidermal proliferation was partially reversed.55... 

Rawlings, A.V. etal. Keratinocyte ceramide synthesis, effect of lactic acid isomers on stratum corneum lipid levels and stratum corneum barrier function, Arch. Dermatol. Res., 288, 383, 1996. 

The EFA metabolism is presented in several extensive reviews.9 16 17 Much of the information concerning EFA physiology and biochemistry has been derived from work in hepatocytes and may be of limited relevance to epidermis since a major role of the liver is to convert dietary lipids into energy stores. Meanwhile, keratinocytes are involved in the fatty acid metabolism required both for normal cellular processes and the specialized role in the permeability barrier. Unlike the liver, the epidermis does not possess the capacity to desaturate at the A5 or A6 position, and therefore the skin relies on a supply of AA, LA, and ALA from the bloodstream. There is evidence for a distinct fatty acid binding protein in keratinocyte plasma membranes that is involved in EFA uptake into the skin and also recycling of free fatty acids from the stratum corneum.18 The transport mechanism in epidermis differs from that in hepatocytes since there is preferential uptake of LA over OA, which may function to ensure adequate capture of LA for barrier lipid synthesis.18... 

Not only biochemical analysis, but immunohistochemical staining with antibodies against gangliosides has similarly revealed the existence and distribution of gangliosides in epidermis. Nakakuma et al. showed that epidermal keratinocytes reacted with an anti-GM3 monoclonal antibody, but not an anti-GD3 mAb.11 Expression of GM3, predominantly in the stratum corneum, was reported by Paller et al.12 In contrast, Hersey et al. detected GD2 in the basal and spinous layers of the epidermis, whereas neither GM3 nor GD3 was detected in normal skin.13 However, the epidermis adjacent to naevi and primary melanoma strongly expressed GD3.13... 

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