title: Examination of changes in connective tissue macromolecular components of large white pig skin following application of Lewisite vapour.
abstract: The aim of this study was to provide information about the degradative processes that occur in major connective tissue components in skin following exposure of large white pigs to Lewisite vapour. Of particular interest were alterations in glycoproteins, which are known to mediate dermo-epidermal attachment (laminin and type IV collagen) and the main collagen found in the dermis (type III collagen). The immunostaining of transfer blots from skin extracts run on sodium dodecyl sulphate polyacrylamide gel electrophoresis gels revealed no evidence of cross-linking of laminin or of type III or IV collagen. However, there was evidence of a very considerable degradation of laminin and, to a lesser extent, of type IV collagen. Type III collagen did not appear to be degraded in skin exposed to Lewisite. These degradative processes appeared to be more severe than found in previous studies in Yucatan mini-pigs percutaneously exposed to sulphur mustard, in which only laminin was found to undergo partial cleavage rather than wholesale degradation. The results suggest that damage to macromolecular components in the sub-epidermal basement membrane in skin which mediate dermo-epidermal separation processes may be a common feature in the mechanism of action of vesicating agents such as Lewisite and sulphur mustard. It is of interest that the damage to laminin in this study appeared to be more severe than that previously found for sulphur mustard. This suggests that skin can suffer substantial damage yet, in the case of Lewisite exposure, recover relatively quickly. However, Lewisite is not an alkylating agent. Sulphur mustard, in contrast, generates characteristically slow healing lesions, most probably because of its ability to alkylate cell types that normally would be involved in skin regenerative processes.
authors.affiliation: Biomedical Sciences Department, Dstl Porton Down, Salisbury, Wilts SP4 0JQ, UK. clindsay@dstl.gov.uk
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lindsay
authors.forename: Joy L
authors.initials: JL
authors.lastname: Hambrook
authors.forename: Roger F R
authors.initials: RF
authors.lastname: Brown
authors.forename: Jan C
authors.initials: JC
authors.lastname: Platt
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Paul
authors.initials: P
authors.lastname: Rice
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000009:adverse effects*; D002619:Chemical Warfare Agents / Q000009:adverse effects*; D024061:Collagen Type III / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D024141:Collagen Type IV / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003238:Connective Tissue / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000187:drug effects* / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D014835:Volatilization
chemical_list: D001152:Arsenicals; D002619:Chemical Warfare Agents; D024061:Collagen Type III; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D007797:Laminin; C035965:lewisite