SULFUR MUSTARD-INCREASED PROTEOLYSIS FOLLOWING IN-VITRO AND IN-VIVO EXPOSURES

The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Papirmeister et al. (1985) postulate enhanced proteolytic activity as a proximate cause of HD-induced cutan eous injury. Using a chromogenic peptide substrate assay, we previousl y reported that in vitro exposure of cell cultures to HD enhances prot eolytic activity. We have continued our investigation of HD-increased proteolytic activity in vitro and have expanded our studies to include an in vivo animal model for HD exposure. In vitro exposure of human p eripheral blood lymphocytes (PBL) to HD demonstrated that the increase in proteolytic activity is both time- and temperature-dependent. Usin g a panel of 10 protease substrates, we established that the HD-increa sed proteolysis was markedly different from thar generated by plasmino gen activator. The hairless guinea pig is an animal model used for the study of HD-induced dermal pathology. When control and HD-exposed PBL and hairless guinea pig skin where examined, similarities in their pr otease substrate reactivities were observed. HD-exposed hairless guine a pig skin biopsies demonstrated increased proteolytic activity that w as time-dependent. The HD-increased proteolytic response was similar i n both in vitro and in vivo studies and may be useful for elucidating both the mechanism of HD-induced vesication and potential treatment co mpounds.