Epidermal-Dermal Junction Basement Membrane

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 

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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. 

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. 

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