IMMUNOHISTOCHEMICAL STUDIES OF BASEMENT-MEMBRANE PROTEINS AND PROLIFERATION AND APOPTOSIS MARKERS IN SULFUR MUSTARD-INDUCED CUTANEOUS LESIONS IN WEANLING PIGS

Sulfur mustard (2,2-dichlorodiethyl sulfide, HD) is a chemical warfare a ent that is a threat to both troops and civilians. The focus of HD research has been on intracellular adduct formation leading to apoptos is and/or necrosis in cutaneous lesions. However, there is work which suggests that HD may have a more direct effect on the basement membran e zone. Immunohistochemical staining to desmosomal proteins, cellular fibronectin, laminin 1, laminin 5, collagen IV: collagen VII, p53; Bcl -2, and PCNA was performed on weanling pig skin exposed to vesicating doses of HD. GB3: an antibody to laminin 5: showed a progressive decre ase with loss of expression during the time period of clinical vesicul ation. The other basement membrane proteins showed no change or incons istent changes. PCNA, and p53 staining increased in the overlying epid ermis in areas of vesiculation without significant necrosis. Bcl-2 pos itive cells were decreased or absent after exposure. This study implic ates laminin 5 as the main basement membrane protein affected acutely by HD exposure. The patterns of staining of PCNA, Bcl-2, and p53 withi n the epidermis suggest that apoptosis and cellular necrosis both may play a role in cell death secondary to HD. (C) 1997 Elsevier Science I reland Ltd.