CUTANEOUS EXPOSURE TO BIS-(2-CHLOROETHYL)SULFIDE RESULTS IN NEUTROPHIL INFILTRATION AND INCREASED SOLUBILITY OF 180,000 M-R SUBEPIDERMAL COLLAGENS

Citation
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
Citations number
48
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
53
Issue
10
Year of publication
1997
Pages
1405 - 1412
Database
ISI
SICI code
0006-2952(1997)53:10<1405:CETBRI>2.0.ZU;2-N
Abstract
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.