Desquamation in the Stratum Corneum

Acta Derm Venereol 2000; Supp 208: 44±45 Desquamation in the Stratum Corneum

TORBJOÈ RN EGELRUD Department of Public Health and Clinical Medicine, Dermatology and Venereology, UmeaÊ University, UmeaÊ, Sweden

To maintain a constant thickness of the stratum corneum the In order to understand desquamation we will have to desquamation rate and the de novo production of corneocytes is identify mechanisms of cell cohesion in the stratum corneum, delicately balanced. Using a plantar stratum corneum model we the structures involved, and the changes these structures have obtained evidence that proteolysis is a central event in the undergo as cell cohesion decreases. We must then identify the desquamation process. A number of regulatory mechanisms for chemical reactions taking place, which would immediately desquamation have been postulated based on our ®ndings. give us information regarding the nature of the involved (Accepted September 20, 1999.) enzymes. Using pieces of plantar stratum corneum we have Acta Derm Venereol 2000; Supp 208: 44±45. developed a simple model system [1] in which some basic Professor TorbjoÈrn Egelrud, MD, Ph.D, Dept. events in desquamation can be studied. In addition to Dermatology, University of UmeaÊ, 90185, UmeaÊ, Sweden. information about the enzyme(-s) involved in stratum E-mail: [email protected] corneum cell dissociation, the system has provided information about the nature of the cohesive structures in the stratum corneum. An important ®nding was that corneocyte cohesion is mediated to a large extent by protein structures, i.e. the modi®ed desmosomes of the stratum corneum [2, 3]. This INTRODUCTION implied that proteolysis may be a central event in desquama- The building blocks of the stratum corneum, the corneocytes, tion. There is good evidence for the involvement of and their intercellular cohesive structures, constitute an proteolytic enzymes in desquamation also in non-palmar- important part of the barrier, and they form a backbone plantar stratum corneum [4, 5]. for the intercellular barrier lipids. There is a continuous production of new stratum corneum. ENZYMES INVOLVED IN DESQUAMATION In order to maintain a constant stratum corneum thickness at a given body site super®cial parts of the stratum corneum The best characterised enzyme so far with a proposed must be continuously shed in the process of desquamation at function in desquamation is stratum corneum chymotryptic a rate which balances de novo production of corneocytes. enzyme (SCCE) [6 ± 9]. SCCE has several properties compa- Desquamation normally occurs invisibly with shedding of tible with a role in desquamation in vivo, including pH pro®le individual cells or small aggregates of cells. Disturbances in of its catalytic activity, its inhibitor pro®le, and tissue this process results in the accumulation on the skin surface of location. SCCE is produced as an inactive precursor which only partially detached cells with or without a concomitant can be converted to active enzyme by proteolytic modi®cation thickening of the stratum corneum. The severity of the by trypsin-like enzymes. The mechanisms of SCCE-activation disturbance may vary from modest to very pronounced, from in vivo remains to be elucidated. a barely visible scaling combined with a feeling of roughness Results of expression analyses suggest that SCCE may be and dryness of the skin surface, to the accumulation of thick skin-speci®c. It is expressed in high suprabasal keratinocytes brittle scales such as in psoriasis or in the various forms of in interfollicular epidermis [10]. In hair follicles and sebaceous ichthyosis. glands it is expressed at sites with corni®ed epithelia [11, 12]. The turnover time of the stratum corneum is normally two Ultrastructural studies have shown that SCCE is present in to four weeks. The mechanisms responsible for a well the stratum corneum extracellular space, to which it is regulated desquamation may be assumed to be very complex. transported during corni®cation [13]. In addition to SCCE A central event in desquamation is elimination of corneocyte there are also other proteases present in the stratum corneum. cohesion. If this took place in the barrier-forming parts of the Of these a 30 kD serine protease with trypsin-like primary stratum corneum it would be deleterious. Corneocytes are substrate speci®city [8] may be of special interest. It has been ``dead'' in the sense that they have no protein synthesis, which postulated to have a complementary role to that of SCCE in means that they have no active turnover of cell surface desquamation [5], and it is a candidate for being responsible structures, and they can not respond to intercellular for the activation of the SCCE-precursor. signalling. Thus, any process within the stratum corneum which leads to structural and functional changes will have to REGULATION OF DESQUAMATION be inititated in one sense or the other by keratinocytes in the viable parts of the epidermis. At the time when the most The mechanisms by which desquamation is regulated remain super®cial part of the the stratum granulosum is transformed to be elucidated. Given the fact that proteolytic degradation to the deepest part of the stratum corneum there must be a of desmosomes may be a central event in desquamation, a ``programming'' of the tissue which allows individual cells to number of possible regulatory mechanisms can be postulated. be strongly linked to each other for a certain period of time, To these belong activation of enzyme precursors, protease after which cell cohesion should decrease to a point where cell inhibitors in the stratum corneum [14], changes in the lipid shedding can occur. composition of the stratum corneum intercellular space [15],

Acta Derm Venereol Supp 208 # 2000 Taylor & Francis. ISSN 0001-5555 Desquamation in the stratum corneum 45 water content [16, 17] and pH of the stratum corneum [18], 7. LundstroÈm A, Egelrud T. Stratum corneum chymotryptic and the action of modifying enzymes such as various enzyme: a proteinase which may be generally present in the glycosidases [19]. stratum corneum and with a possible involvement in desquamation. Acta Derm-Venereol (Stockh) 1991; 71: 471 ± 474. 8. Egelrud T. Puri®cation and preliminary characterization of CONCLUSION stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. J Invest Dermatol 1993; 101: 200 ± A well regulated desquamation is a prerequisite for the barrier 204. function of the stratum corneum and for a normal skin 9. Hansson L, StroÈmqvist M, BaÈckman A, Wallbrandt P, Carlstein appearance. In recent years we have learnt some basic facts A, Egelrud T. Cloning, expression, and characterization of about stratum corneum cell cohesion and the role of stratum corneum chymotryptic enzyme, a skin-speci®c human proteolytic enzymes in desquamation. Our knowledge in serine proteinase. J Biol Chem 1994; 269: 19420 ± 19426. this area is, however, still very limited. In the near future we 10. Sondell B, Thornell L-E, Stigbrand T, Egelrud T. Immunolcoa- may expect to discover a number of hitherto unknown lization of stratum corneum chymotryptic enzyme in human skin enzymes and enzyme inhibitors involved. We may also expect and oral epithelium with monoclonal antibodies: evidence of a to learn from studies on hereditary skin diseases with proteinase speci®cally expressed in keratinizing squamous epithe- disturbances in the formation and turnover of the stratum lia. J Histochem Cytochem 1994; 42: 459 ± 465. corneum. And, of course, studies on the stratum corneum 11. Ekholm E, Sondell B, Dyberg P, Jonsson M, Egelrud T. carried out by biophysicists will continue to provide crucial Expression of stratum corneum chymotryptic enzyme in normal human sebaceous follicles. Acta Derm Venereol (Stockh) 1998; information, not only for the understanding of the barrier 78: 343 ± 347. properties of the stratum corneum, but also for the under- 12. Ekholm E, Egelrud T. The expression of stratum corneum standing of desquamation. chymotryptic enzyme in human anagen hair follicles. Further evidence for its involvement in desquamation-like processes. Br REFERENCES J Dermatol 1998; 139: 585 ± 590. 13. Sondell B, Thornell L-E, Egelrud T. Evidence that stratum 1. LundstroÈm A, Egelrud T. Cell shedding from human plantar skin corneum chymotryptic enzyme is transported to the stratum in vitro: evidence of its dependence on endogenous hydrolysis. corneum extracellular space via lamellar bodies. J Invest J Invest Dermatol 1988; 91: 340 ± 343. Dermatol 1995; 104: 819 ± 823. 2. LundstroÈm A, Egelrud T. Evidence that cell shedding form 14. Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O. plantar skin in vitro involves endogenous proteolysis of the the Antileukoprotease inhibits stratum corneum chymotryptic desmosomal protein desmoglein I. J Invest Dermatol 1989; 94: enzyme. Evidence for a regulative function in desquamation. 216 ± 220. J Biol Chem 1996; 271: 21886 ± 2189. 3. Egelrud T, LundstroÈm A. Immunochemical analyses of the 15. Williams ML. Lipids in normal and pathological desquamation. distribution of the desmosomal protein desmoglein I in different Adv Lipid Res 1991; 24: 211 ± 262. layers of plantar epidermis. Acta Derm Venereol (Stockh) 1989; 16. Warner RR. Water content from analysis of freeze-dried thin 69: 470 ± 476. section. J Microsc 1986; 142: 363 ± 369. 4. Egelrud T, LundstroÈm A. The dependence of detergent-induced 17. von Zglinicky T, Lindberg M, Roomans GM, Forslind B. Water cell dissociation in non-palmo-plantar stratum corneum on and ion distribution pro®les in human skin. Acta Derm Venereol endogenous proteolysis. J Invest Dermatol 1990; 95: 456 ± 459. (Stockh) 1993; 73: 340 ± 343. 5. Suzuki Y, Nomura J, Koyama J, Takahashi M, Horii I. 18. OÈ hman H, Vahlquist A. In vivo studies concerning a pH gradient Detection and characterization of endogenous protease associated in human stratum corneum and upper epidermis. Acta Derm with desquamation of stratum corneum. Arch Dermatol Res Venereol (Stockh) 1994; 74: 375 ± 379. 1993; 285: 372 ± 377. 19. Walsh A, Chapman SJ. Sugars protect desmosome and corneo- 6. Egelrud T, LundstroÈm A. A chymotrypsin-like proteinase that some glycoproteins from proteolysis. Acta Dermatol Res 1991; may be involved in desquamation in plantar stratum corneum. 283: 174 ± 179. Arch Dermatol Res 1991; 283: 108 ± 112.

Acta Derm Venereol Supp 208