Assessment of the biochemical effects of percutaneous exposure of sulphur mustard in an in vitro human skin system.
1. Sulphur mustard (HD) is a potent chemical warfare agent which causes incapacitating blisters on human skin. There is no specific pretreatment nor therapy against this agent and the mechanism of dermo-epidermal cleavage is unclear. The aim of this study was to use a human skin explant system to determine the consequences of percutaneous exposure to HD. 2. Increased activities of serine proteases associated with blistering disorders in humans were detected from human skin explants after exposure to HD. The most consistent response and the highest protease activities measured were found for trypsin. This class of enzyme is therefore implicated in the dermo-epidermal separation which is associated with blistering in humans following exposure to HD. 3. An inflammatory response was observed in the skin explants exposed to HD. At low doses of HD it was characterised by the presence of neutrophils in the papillary dermis, culminating in the infiltration of the epidermis by these inflammatory cells at higher concentrations of HD. A variety of other histopathological changes in the explants was found such as focal dermo-epidermal separation, nuclear pyknosis and perinuclear vacuolation. 4. The study indicates that full thickness human skin explants can be used to investigate various aspects of the possible pathogenesis of HD-induced skin damage, including the associated inflammatory response.
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Chemical and Biological Defence Establishment, Salisbury, Wiltshire, UK.
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D000287:Administration, Topical; D000367:Age Factors; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D010450:Endopeptidases / Q000032:analysis; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D009151:Mustard Gas / Q000008:administration & dosage* / Q000633:toxicity*; D009924:Organ Culture Techniques; D010269:Paraquat / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
D010450:Endopeptidases; D010269:Paraquat; D009151:Mustard Gas