Physiology of the skin

Keratinocyte maturation

The differentiation of basal cells into dead, but functionally important, corneocytes is a unique feature of the skin. The horny layer is important in preventing all manner of agents from entering the skin, including microorganisms, water and particulate matter. Antimicrobial peptides of the defensin and cathelicidin classes, present on the epidermal surface, have antibacterial and antiviral activity. The epidermis also prevents the body’s fluids from getting out.

Epidermal cells undergo the following sequence during keratinocyte maturation ( Fig. 3.1 ):

• 1.

  Stem cells in the basal layer divide (continuously) into one new stem cell and a transit amplifying cell. Transit amplifying cells proliferate briefly and then progress upwards and undergo terminal differentiation.

• 2.

  In the prickle cell layer , cells change from being columnar to polygonal. Differentiating keratinocytes synthesize keratins, which aggregate to form tonofilaments. The desmosomes connecting keratinocytes are composed of the structural molecules cadherins, desmogleins and desmocollins. Desmosomes distribute structural stresses throughout the epidermis and maintain a distance of 20 nm between adjacent cells.

• 3.

  In the granular layer , enzymes induce degradation of nuclei and organelles. Keratohyalin granules containing filaggrin provide an amorphous protein matrix for the tonofilaments. Membrane-coating granules attach to the cell membrane and release an impervious lipid-containing cement, which contributes to cell adhesion and to the horny layer barrier.

• 4.

  In the horny layer , the dead, flattened corneocytes have developed thickened cornified envelopes containing involucrin that encase a matrix of keratin macrofibres aligned by filaggrin. The strong disulphide bonds of the keratin provide strength to the stratum corneum, but the layer is also flexible and can absorb up to three times its own weight in water. However, if it dries out (i.e. water content falls below 10%), pliability fails.

• 5.

  The corneocytes are eventually shed from the skin surface after degradation of the lamellated lipid and loss of desmosomal intercellular connections.