Changes in connective tissue macromolecular components of Yucatan mini-pig skin following application of sulphur mustard vapour.

1. The aim of this study was to determine the nature of the macromolecular alterations in Yucatan mini-pig skin which occur following application of sulphur mustard vapour, with particular reference to laminin and type IV collagen. 2. The immunostaining of transfer blots from skin extracts run on SDS-PAGE gels revealed no evidence of cross-linking of type IV collagen or laminin. Laminin was, however, found to be partially degraded as determined by the resolution of 132 and 143 kDa fragments, possibly by the activation of proteases, following the application of sulphur mustard to pig skin. Type IV collagen was not subject to this form of degradation in the skin samples exposed to sulphur mustard. 3. Yucatan mini-pig skin was found to develop microblisters after exposure to sulphur mustard vapour. The immunohistochemical studies of sulphur mustard exposed skin revealed that separation of the epidermis from the dermis was found to occur within the lamina lucida of the subepidermal basement membrane, supporting the contention that cleavage of laminin networks occurs following mustard challenge. Immunohistochemical staining with anti-type IV collagen antibodies was restricted to the floor of the micro-blister lesions. 4. The results suggest that laminin may be a target for protease activation at the dermo-epidermal junction. This may account for the tendency of certain skin models to develop sulphur mustard-induced blistering. The Yucatan mini-pig may be valuable as a model to determine the efficacy of prophylactic and therapeutic regimes.