Corneodesmosomes

The outermost layer of the skin, the cornified layer or stratum corneum, has been identified as the principal diffusion barrier for substances, including water [2,3]. It is approximately 10 to 20 pm thick when dry but swells to several times this thickness when fully hydrated [17], It contains 10 to 25 layers lying parallel to the skin surface of nonviable cells, the corneocytes, which are surrounded by a cell envelope and imbedded in a lipid matrix. This architecture is often modeled as a wall-like structure, with the corneocytes as protein bricks embedded in a lipid mortar [18]. Similarly to the viable epidermis, desmosomes (corneodesmosomes) contribute to the cell cohesion. 

Results from enzymologic studies have suggested that SCCE has an extracellular localization in the stratum corneum.45 This has been corroborated by means of immunoelectron microscopy. With this method SCCE was found intracellularly in association with lamellar bodies in the stratum granulosum. In the transition between the stratum granulosum and the stratum corneum, SCCE is extruded to the extracellular space together with the lamellar bodies. In the stratum corneum specific labeling is found only in the extracellular space, often in association with corneodesmosomes.46... 

We are very far from an understanding of how and by which mechanisms desquamation is regulated. If we assume, however, that proteolytic degradation of corneodesmosomes plays a major role in desquamation, a number of possible mechanisms can be postulated on the basis of the present knowledge. These are summarized in Table 7.1. 

The activation of enzyme precursors is likely to be of central importance. A significant fraction of the total SCCE present in the stratum corneum is in the form of inactive proenzyme.53,54 A change in the ratio of precursor to active enzyme may be expected to cause marked changes in the rate of corneodesmosomal degradation. In vitro pro-SCCE can be activated by pancreatic trypsin.39 As mentioned earlier SCTE has been suggested to act as an SCCE activator, but this remains to be elucidated. It is possible that SCCE is just one of a number of enzymes constituting a proteolytic cascade in the stratum corneum, in which one enzyme serves as activator of another enzyme. 

As described earlier, although water (i.e., moisturization) is required to alleviate dry skin, reduced enzymic activity is the cause of the scaling symptoms associated with the condition. These enzymes can be activated for instance with glycerol,31 hydroxyacids,25 or urea,32 but to retain full desquama-tory activity topical application of enzymes is required. As all corneodesmosomal proteins persist in the superficial layers of the SC in dry skin, either the full spectrum of skin desquamatory enzymes are required to maximally induce exfoliation or broad specificities are needed in a single enzyme. 

Enzyme diffuses towards corneodesmosomes to begin their degradation and encapsulation with barrier lipids, transformation of fragile to resilient corneocyte... 

Intact corneodesmosomes and normal lipid bilayers, filaggrin hydrolysis dependent on water activity... 

D = Corneodesmosome E = Stratum corneum enzymes e = Intracellular enzymes... 

Intact corneodesmosomes, reduced enzyme activity, lipid disruption, decreased lipids leading to abnormal barrier function, excessive loss of NMF retention of fragile corneocyte phenotype... 

Intact corneodesmosomes and lipid disruption, lack of maturation of corneocytes reduced Tgase activity... 

D= Corneodesmosome E= Stratum corneum enzymes e=lntracellular enzymes... 

FIGURE 17.8 Effect of topically applied Optimase on corneodesmosome degradation in vitro. From El-Kadi, K., Rawlings, A.V., Feinberg, C., Nunn, C., Battaglia, A., Chandar, P., Richardson, N., Sabin, R., and Pocalyko, D. Arch. Dermatol. Res., 293, 500-507, 2001. 

Caubet, C. et al. Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, J. Invest. Dermatol., 122, 1235-1244, 2004. 

Simon, M., Bernard, D., Minondo, A.M., Camus, C., Fiat, F., Corcuff, P., Schmidt, R., and Serre, G. Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin, J. Invest. Dermatol., 116, 23-30, 2001. 

Clearly in dry flaky skin conditions where corneodesmosome degradation is frequently and characteristically perturbed then generation of amino acid-derived intercellular humectancy will also be decreased potentially leading to a further reduction in protease activity. 

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