SULFUR MUSTARD INCREASES ELASTASE-LIKE ACTIVITY IN HOMOGENATES OF HAIRLESS GUINEA-PIG SKIN

The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Enhanced proteolytic activity has bee n postulated as the cause of HD-induced dermal epidermal. separation. Using a chromogenic assay, we previously reported that HD-exposed hair less guinea pig skin biopsies demonstrated increased proteolysis of th e peptide substrate Tosyl-gly-pro-arg-p-nitroanilide, Chromozym TH (TH ). Elastase activity has been used as a biomarker of inflammation in s kin. In this study we assayed human leukocyte elastase (HLE) and solub le extracts of biopsies from control and HD-exposed hairless guinea pi g skin with both the TH and the HLE (N-methoxysuccinyl-ala-ala-pro-val -p-nitroanilide) substrates. HD-increased proteolysis of both substrat es indicates that multiple enzymes may contribute to HD-induced pathol ogy. The increased activities of an inflammation-associated enzyme suc h 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 earli er than previously thought. The presence of HD-increased proteolysis i n a soluble extract should facilitate further characterization of the proteolytic activity and may be useful for elucidating both the mechan ism(s) of HD-induced pathology and potential treatment compounds.