ABSTRACT
Skin, the largest organ in the body, provides a multitude of protective, metabolic, and immunological functions. These include physical separation between the internal and external environments, regulation of temperature, biosynthesis of biologically important compounds, and participation in several types of inflam-
and immune reactions (for review, see Ref. 11). Basically, the skin is composed of epidermis, dermis, and subcutis (Figure 1). The epidermis forms a stratified squamous epithelium consisting of several cell including keratinocytes, Langerhans cells, and melanocytes. By far, the most abundant cell type is the keratinocyte, which undergoes maturation eventually resulting in terminal differentiation, e.g., formation of dead corneocytes at the skin surface
The keratinocytes arise as basal cells at the lower border (basal membrane zone) of epidermis, and following cell division some progeny remain in the basal
as stem cells while others migrate to the overlying epidermal layers and begin to differentiate. During their transition keratinocytes change dramatically both biochemically and morphologically. The most conspicuous changes include (a) cell i1attening and enlargement, (b) synthesis of various intermediate filaments (cytokeratins), (c) appearance of various intracellular bodies (membrane-coating
granules, keratohyalin granules, Odland bodies, etc.), some of which eventually extrude their contents into the intracellular space, and finally (d) disintegration of cellular organelles and formation of a crosslinked envelope of protein covered lipids (for review, see Ref. At the steady state, a number of cells to that of the desquamated cells are in the basal layer. Under normal conditions the time required for a cell to reach the stratum corneum is about 3 weeks with an additional 2-3 weeks before desquamation, yielding a total transit time of about 5-6 weeks. The transit period is reduced to a few days following maximal mitotic stimulation as seen in wounded skin or psoriatic lesions (see below). The thickness of the epidermis (0.15-1.5 mm) is determined both by the number of dividing basal cells and by the cohesiveness of corneocytes. Keratinocytes hold together firmly by desmosomes present in the entire epidermis. In addition, intercellular lipids mainly composed of acyl ceramides and cholesterol contribute to cell cohesion in the horny layer. The process of detachment of corneocytes is not solely a spontaneous event but requires both proteolysis of desmosomes and modification of intercellular lipids (13,14).
