Structural changes of human epidermis induced by human leukocyte-derived proteases

During the process of inflammation human neutrophils release potent serine proteases, such as human leukocyte elastase and cathepsin G. In psoriasis these enzymes are released within the epidermis. To investigate the destructive potential of neutrophil-derived serine proteases these were applied on viable human epidermis as well as full thickness human skin in vitro. Human leukocyte elastase and cathepsin G were found to dissociate keratinocytes from epidermal sheets in a time- and dose-dependent fashion. Significant keratinocyte dissociation was observed 4 h after application of 3 nM human leukocyte elastase. By electron microscopy of elastase- or cathepsin G-treated full thickness human skin, widening of the extracellular space followed by complete separation of keratinocytes without intradesmosomal cleavage was observed. In addition, cathepsin G induced membrane damage as well as destruction of intracellular organelles. Thus, neutrophil-derived serine proteases exert pronounced destructive potential in human epidermis in concentrations likely to appear in lesional psoriatic skin.