title: Characterization of the initial response of engineered human skin to sulfur mustard.
abstract: We have used a new approach to identify early events in sulfur mustard-induced, cutaneous injury by exposing human, bioengineered tissues that mimic human skin to this agent to determine the morphologic, apoptotic, inflammatory, ultrastructural, and basement membrane alterations that lead to dermal-epidermal separation. We found distinct prevesication and post-vesication phases of tissue damage that were identified 6 and 24 h after sulfur mustard (SM) exposure, respectively. Prevesication (6 h) injury was restricted to small groups of basal keratinocytes that underwent apoptotic cell death independent of SM dose. Immunoreactivity for basement membrane proteins was preserved and basement membrane ultrastructure was intact 6 h after exposure. Dermal-epidermal separation was seen by the presence of microvesicles 24 h after SM exposure. This change was accompanied by the dose-dependent induction of apoptosis, focal loss of basement membrane immunoreactivity, increase in acute inflammatory cell infiltration, and ultrastructural evidence of altered basement membrane integrity. These studies provide important proof of concept that bioengineered, human skin demonstrates many alterations previously found in animal models of cutaneous SM injury. These findings further our understanding of mechanisms of SM-induced damage and can help development of new countermeasures designed to limit the morbidity and mortality caused by this chemical agent.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook, New York 11794-8702, USA.
authors.forename: Shari
authors.initials: S
authors.lastname: Greenberg
authors.forename: Padmaja
authors.initials: P
authors.lastname: Kamath
authors.forename: John
authors.initials: J
authors.lastname: Petrali
authors.forename: Tracey
authors.initials: T
authors.lastname: Hamilton
authors.forename: Jackie
authors.initials: J
authors.lastname: Garfield
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Garlick
mesh_terms: D000818:Animals; D017209:Apoptosis; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D023822:Tissue Engineering
chemical_list: D009151:Mustard Gas