Characteristics of Skin Inflammatory Cells Following Exposure of Mice to Sulfur Mustard

Sulfur mustard (SM) is a chemical warfare agent that causes skin damage characterized by inflammation and blistering. We investigated leukocyte infiltration into mouse skin after SM exposure. The dorsal skin of female SKH1‐Hr hairless mice was treated with SM vapor and skin biopsies collected at 1, 3, 5, 7, 14 and 21 days. One day post SM, epidermal thickening and stratum corneum shedding were noted. This was associated with an accumulation of neutrophils (Ly6g+ cells) and macrophages (F4/80+ cells) in the dermis and subcutaneous fat. CCR2, a C‐C chemokine receptor important in macrophage chemotaxis was also expressed in the dermis and hypodermis. By 3 days post‐exposure, there was a 150% increase in wound thickness; this correlated with increased numbers of Ly6g+ and HMGB1+ (inflammatory cytokine) cells in the eschar, and CCR2+ inflammatory cells in the dermis. After 5 days, wound thickness increased 250% of control with pyknotic nuclei in the basal layer, along with increased F4/80+, CCR2+ and HMGB1+ cells in the dermis. By 7 days, a neo‐epidermis had formed along with decreases in Ly6g+ cells. Expression of F4/80+, CCR2+ and HMGB1+ cells decreased 14 days post‐exposure. After 21 days, decreased wound thickness was associated with decreased Ly6g+, F4/80+, CCR2+ and HMGB1+ expressing dermal cells which returned to control levels. These data indicate that SM‐induced skin damage is associated with an early infiltration of neutrophils followed by the accumulation of macrophages in the skin; macrophages are likely important in controlling wound healing. Support: APS 2014 UGSRF; NIH AR055073.