Expression of Laminin 332 in Vesicant Skin Injury and Wound Repair

Sulfur Mustard (SM) is a potent vesicant or blistering agent. It is a highly reactive bi-functional alkylating agent that cross links proteins, DNA, and other cellular components. Laminin 332 is a heterotrimer glycoprotein and a crucial skin component that attaches the epidermal basal keratinocytes to the dermis. SM wounds histologically appear similar to Epidermolysis Bullosa (EB), human genetic blistering diseases that involve genetic changes in laminin 332. The specific mechanism of action of SM exposure is unknown, but there are several key similarities between vesicant induced cutaneous injury and the Junctional form of EB (JEB) cutaneous injury: 1) Initial alkylation causes blistering similar to JEB; 2) Initial injury is followed by protease activation and prolonged inflammation similar to the chronic inflammation observed in EB; 3) The blister plane is at the level of the lamina lucida in the Basement Membrane Zone (BMZ) for both JEB and SM-induced injury. This suggests that injury induced by vesicants is not unique and probably involves malformation of laminin 332. Understanding the role of laminin 332 in SM induced blisters may provide perspectives for future molecular therapeutic countermeasures against SM exposure.