Na. Monteiro-riviere et al., Immunohistochemical characterization of the basement membrane epitopes in bis(2-chloroethyl) sulfide-induced toxicity in mouse ear skin, J APPL TOX, 19(5), 1999, pp. 313-328
Sulfur mustard (bis(2-chloroethyl) sulfide (HD)), a potent cutaneous vesica
nt and bifunctional alkylating agent, produces significant time-dependent h
istopathological changes in the skin of the mouse. The right ears of male C
D1 mice were exposed topically to 5.0 mu l of 195 mM (0.16 mg) HD in dichlo
romethane and harvested at 6, 12, 18 and 24 h. The left ear control was dos
ed with 5.0 mu l of dichloromethane. In all controls and HD-treated mouse e
ar, moderate immunofluorescence staining was seen at the epidermal-dermal j
unction with bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA)
and laminin (Lam), and light staining was observed with bullous pemphigoid
180 (BP180), fibronectin (Fn) and type IV collagen (Coll IV). Mouse anti-h
uman monoclonal antibodies for GB3, L3d and 19-DEJ-1 (Uncein) did not cross
-react. In microvesicles, BP, BP180 and Fn showed areas of light focal epid
ermal staining and homogeneous dermal staining, and EBA, Lam and Coll IV sh
owed moderate dermal staining. Both BP and Fn exhibited weak, inconsistent
staining with time. Immunoelectron microscopy (IEM) revealed similar result
s, with an increase in cell damage from 6 to 24 h, which corresponded to a
decrease in staining intensity. Cell proliferation, expressed as the growth
fraction of proliferating cell nuclear antigen (PCNA), showed an increase
in cell damage. The growth fraction was lower in the inner ear and showed t
ime-dependent differences. The immunofluorescence and IEM results indicate
that HD causes an undulating inconsistent separation in the uppermost lamin
a lucida with focal cleavage into the lower portion of the basal keratinocy
tes just above the plasma membrane. Although this pattern of separation dif
fers from other in vivo models in which the split occurs exclusively within
the lamina lucida, this should not preclude its role as a screening model
to study the effects and development of specific prophylactic and therapeut
ic strategies. Copyright (C) 1999 John Wiley & Sons, Ltd.