Sulfur Mustard Increases Elastase-Like Activity in Homogenates of Hairless Guinea Pig Skin

Abstract

The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Enhanced proteolysis activity has been postulated as the cause of HD-induced dermal epidermal separation. Using a chromogenic assay, we previously reported that HD-exposed hairless guinea pig skin biopsies demonstrated increased proteolysis of the peptide substrate Tosyl-gly-pro-arg-p-nitroanilide, Chromozym TH (TH). Elastaise activity has been used as a biomarker of inflammation in skin. In this study we assayed human leukocyte elastase (HLE) and soluble extracts of biopsies from control and HD-exposed hairless guinea pig skin with both the TH and the HLE (N-methoxysuccinyl-ala-ala-pro-val-p-nitroanilide) substrates. HD-increased proteolysis of both substrates indicates that multiple enzymes may contribute to HD-induced pathology. The increased activities of an inflammation-associated enzyme such as elastase as early as 3-6 hr after HD exposure of hairless guinea pig skin indicate that inflammation may be present in HD lesions earlier than previously thought. The presence of HD-increased proteolysis in a soluble extract should facilitate further characterization of the proteolytic activity and may be useful for elucidating both the mechanism(s) of HD-induced pathology and potential treatment compounds.