Cb. Millard et al., CUTANEOUS EXPOSURE TO BIS-(2-CHLOROETHYL)SULFIDE RESULTS IN NEUTROPHIL INFILTRATION AND INCREASED SOLUBILITY OF 180,000 M-R SUBEPIDERMAL COLLAGENS, Biochemical pharmacology, 53(10), 1997, pp. 1405-1412
Exposure to bis-(2-chloroethyl)sulfide (BCES; ''sulfur mustard'') caus
es delayed formation of slowly healing skin blisters. Although the his
topathology of BCES injury is well characterized [reviewed in Smith et
al., J Am Acad Dermatol 32: 767-776, 1995], little is known of the cu
taneous toxicity at the molecular level. To identify biological marker
s 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 electrophores
is, and lectin- and antisera-binding. Inflammation was assessed by mea
suring edema and myeloperoxidase activity. Edema reached peak levels a
t 15-18 hr and remained elevated above controls at 24 hr. Recruitment
of neutrophils, deduced from increased myeloperoxidase, occurred as ea
rly 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 M-r polyp
eptides in subepidermal protein extracts from the BCES exposed skin ob
tained greater than or equal to 12 hr after exposure. This alteration
was not found in epidermal protein extracts prepared from the same ani
mals. Based upon the determined amino acid compositions, both polypept
ides had significant collagenous triple helical content (>75%). They c
ould 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 epi
dermal-dermal separation and selective alterations of the subepidermal
extracellular matrix. Published by Elsevier Science Inc.