title: Cutaneous exposure to bis-(2-chloroethyl)sulfide results in neutrophil infiltration and increased solubility of 180,000 Mr subepidermal collagens.
abstract: Exposure to bis-(2-chloroethyl)sulfide (BCES; "sulfur mustard") causes delayed formation of slowly healing skin blisters. Although the histopathology of BCES injury is well characterized [reviewed in Smith et al., J Am Acad Dermatol 32: 767-776, 1995], little is known of the cutaneous toxicity at the molecular level. To identify biological markers of exposure, epidermal and subepidermal extracts were prepared from 48 individual hairless guinea pigs (HGP) at successive 3-hr intervals following exposure to BCES vapor, and compared using gel electrophoresis, and lectin- and antisera-binding. Inflammation was assessed by measuring edema and myeloperoxidase activity. Edema reached peak levels at 15-18 hr and remained elevated above controls at 24 hr. Recruitment of neutrophils, deduced from increased myeloperoxidase, occurred as early as 3 hr after BCES exposure with maximum infiltration at 6-12 hr. Binding of concanavalin-A lectin revealed increased amounts, relative to contralateral control sites, of two approximately 180,000 Mr polypeptides in subepidermal protein extracts from the BCES-exposed skin obtained > or = 12 hr after exposure. This alteration was not found in epidermal protein extracts prepared from the same animals. Based upon the determined amino acid compositions, both polypeptides had significant collagenous triple helical content (>75%). They could be distinguished immunologically from collagen types I, III, and IV by using polyclonal antisera. We conclude that exposure of HGP skin to BCES results in an early neutrophil infiltration that precedes epidermal-dermal separation and selective alterations of the subepidermal extracellular matrix.
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, U.S.A.
authors.forename: C B
authors.initials: CB
authors.lastname: Millard
authors.forename: R
authors.initials: R
authors.lastname: Bongiovanni
authors.forename: C A
authors.initials: CA
authors.lastname: Broomfield
mesh_terms: D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001768:Blister / Q000139:chemically induced; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003208:Concanavalin A / Q000378:metabolism; D004487:Edema / Q000139:chemically induced; D006168:Guinea Pigs; D007106:Immune Sera / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009151:Mustard Gas / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility
chemical_list: D000596:Amino Acids; D007106:Immune Sera; D003208:Concanavalin A; D003094:Collagen; D009195:Peroxidase; D009151:Mustard Gas