Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical WarfareabepepbcbcbcdmvcdmbbcpmnmvFig 8-10. Transmission electron microscopy of hairless guinea pig skin. (a) Unexposed skin site at the level of the dermalepidermaljunction; epidermis (ep), basal cells of the stratum germinativum (bc), dermis (d). (b) Skin site exposed to sulfurmustard vapor 4–6 h postexposure; basal cell (bc) undergoing early apoptotic injury with marginal condensation of chromatinand formation of a microvesicle (mv) within the microenvironment of the basement membrane zone. (c) Skin siteexposed to sulfur mustard vapor 24 h postexposure; disabling of hemidesmosomes (arrows) contributing to the formationof characteristic microvesicles (mv), basal cells undergoing advanced apoptotic injury and necrosis (bc). (d) The cavity of alarge microblister (mb) infiltrated with polymorphonucleocytes (pmn).Photographs (a, b, and d): Courtesy of John P Petrali, PhD, US Army Medical Research Institute of Chemical Defense, andStephanie R Froberg, Graphics Department, US Army Medical Research Institute of Chemical Defense, Aberdeen ProvingGround, Md. Photograph (c) reproduced with permission from: Marlow DD, Mershon MM, Mitcheltree LW, Petrali JP, JaaxGP. Sulfur mustard-induced skin injury in hairless guinea pigs. J Toxicol Cutan Ocular Toxicol. 1990;9(3): 179–192.teristic microvesicles within the lamina lucida of thebasement membrane. The cavities of microvesiclesformed as a consequence of basal cell pathology andthe disabling of anchoring filaments of hemidesmosomesare bound by degenerating epidermal cellsat the roof and by the lamina densa of the basementmembrane at the floor. Microvesicles rapidly becomeinfiltrated with inflammatory cells, phagocytic cells,degenerating cells, cellular debris, and tissue fluid, allexacerbating the lesion to form pervasive lucidolyticmicroblisters that later cleave the epidermis from thedermis (Figure 8-11).Furthermore, investigative evidence shows thatpercutaneous carriers such as dimethyl sulfoxide canexacerbate mustard-gas–induced skin pathology. 83Ultrastructural studies of monotypic human cellsin culture, such as keratinocytes and lymphocytes,have added important subcellular information of HDtemporal effects on nuclei, plasma membranes, andcytoplasmic organelles, perhaps reflecting predictedand expected biochemical lesions reported elsewherein this chapter.Skin proteins and immunohistopathology. Primaryor secondary effects of HD toxicity on extracellularcomponents of the basement membrane microenvironmentare presently under investigation. Among theseextracellular domains are structural adherent proteinsknown to be antigenically altered or lost to specificantisera in some clinical bullous diseases. 84 Althoughstill the subject of study, proteins shown to be altered272