Dermal-epidermal junction

Epidermis Complete removal of the dermis may be achieved by several mechanical, thermal, and chemical techniques. Most commonly, the epidermal-dermal junction is split by heating the skin to 60 C for 30-120 s [83, 84], Pitman et al. [85] could show that such a treatment does not impair the barrier function. The use of ethylene diamine tetraacetic acid, sodium bromide, or ammonia fumes has also been reported [80, 83, 86], It may, however, be suspected that the use of sufficiently strong acids or bases may change the buffer capacity of skin, which would especially influence the penetration behavior of ionizable drugs. 

Fig. 1. (A) Scanning electron micrograph of human skin. The epidermis has pulled away from part of the basement membrane. (B and C) Transmission electron micrograph through the epidermal-dermal junction of human skin. Keratinocytes (KF) are the cells in the human epidermis. LD, The lamina densa of the basement membrane LL, the lamina lucida. Typical anchoring fibrils (AF) formed from type VII collagen are shown at higher power in C. Courtesy of Dr. K. Holbrook, University of Washington.

The boundary between the epidermis and dermis is a basement membrane (see Figure 3.9) it can be described by four planes proceeding from the basal epidermal side to the dermal side (a) the border of the basal ker-atinocyte (b) the lamina lucida, an electron lucent layer that lies beneath the epidermis (c) the lamina densa, an electron dense layer also known as the basal lamina and (d) the reticular lamina or subepidermal zone consisting of connective tissue immediately below the epidermis. The mechanical continuity at the epidermal-dermal junction, as well as between keratinocytes, is key to normal transfer of internal and external mechanical forces between the epidermis and dermis. 

Thus, external forces applied to the epidermis and/or internal forces present in dermis are transmitted through the cornified layer and lead to stretching of keratinocyte-keratinocyte cell junctions and the epidermal-dermal junction. These forces appear to be transmitted between epithelial cells via cadherins and may result in activation of secondary messengers which alter gene expression and protein synthesis. 

The final type of chemical toxicity that will be presented are the vesicants, chemicals that cause blisters on the skin. There are two classes of blisters that implicate different mechanisms of vesication. Intraepidermal blisters are usually formed due to the loss of intercellular attachment caused by cytotoxicity or cell death. The second class occurs within the epidermal-dermal junction (EDJ) due to chemical-induced defects in the basement membrane components. The classic chemical associated with EDJ blisters is the chemical warfare agent sulfur mustard (bis-2-chloroethyl sulfide HD). HD is a bifunctional alkylating agent that is highly reactive with many biological macromolecules, especially those containing nucleophilic groups such as DNA and proteins. 

Experimental evidence suggests that, after SM exposure, alkylation and crosslinking of matrix molecules at the epidermal-dermal junction could adversely affect the abihty of the epithelium to tack down once again to the... 

Monteiro-Riviere, N.A., Inman, A.O. (1995). Indirect immuno-histochemistry and immunoelectron microscopy distribution of eight epidermal-dermal junction epitopes in the pig and in isolated perfused skin treated with bis (2-chloroethyl) sulfide. 

Briggman, RA., Schechter, N.M., Fraki, J.E. and Lazarus, G.S. (1984). Degradation of the epidermal-dermal junction by a proteolytic enzyme from human skin and human polymorphonuclear leukocytes. J. Exp. Med. 160, 1027—1042. 

Once the skin is exposed, blisters develop after a period of itching and erythema, with the basal epidermal cell as the key cellular target of sulfur mustard in skin. By light microscopy, nuclear swelling begins within 3 to 9 hr after exposure, followed by nuclear pyknosis and vacuolation of cytoplasm. Edema at the epidermal-dermal junction is seen within 12 hr of exposure, and by 16 hr there is separation, with formation of coalescing vesicles. Blisters break and denude during the first week after exposure, and new blisters may form near others that are well developed. 

FIGURE 18.1 Primary vulvar Paget disease (A). (H E.) Tumor cells express CK7 (B) and GCDFP (C), but normal epithelium does not. Occult stromal invasion can be highlighted by CK7 (D) when inflammation obscures the epidermal-dermal junction. 

Due to the highly reactive nature of mustard, it is conceivable that the injury following tissue exposure may result from a combination of effects described below in both hypotheses or injury may result from additional changes not yet described in a formal hypothesis. Whether the initiating event is alkylation of DNA or modification of other cellular macromolecules, however, these steps would disrupt the epidermal-dermal junction. Once the site of tissue injury is established, the pathogenic process leading to formation of fully developed blisters must involve an active inflammatory response and altered fluid dynamics in the affected tissue. 

The basement membrane zone or epidermal-dermal junction is a thin extracellular matrix that separates the epidermis from the dermis. It is a highly specialized structure recognized with the light microscope as a thin, homogeneous band. Ultra-structurally, it can be divided into four component layers (1) the cell membrane of the basal epithelial cell, which includes the hemidesmosomes (2) the lamina ludda (lamina rara) (3) the lamina densa (basal lamina) and (4) the subbasal lamina (sublamina densa or reticular lamina), with a variety of fibrous structures (anchoring fibrils, dermal microfibril bundles, microthreadlike filaments) (Briggaman and Wheeler, 1975). The basement membrane has a complex molecular architecture with numerous components that play a key role in adhesion of the epidermis to the dermis. The macromolecules that are ubiquitous components of all basement membranes... 

Briggaman, R.A. (1990). Epidermal-dermal junction Stracture, composition, function and disease relationships. Prog. Dermatol., 24 1-8. 

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