Epidermal-dermal junction components

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. 

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... 

A major problem encountered with Epicel has been epidermal blistering. Small blisters may resolve spontaneously, but larger blisters result in graft failure [34]. This phenomenon has been attributed to absence of dermal-epidermal junction components at grafting. Despite this limitation, the availabihty of Epicel has provided a much needed treatment option for patients with massive burns where donor skin for autograft is extremely limited [34]. 

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