Vesicant Exposed Wound Healing

Hepatocyte Growth Factor Enhances Wound Healing Vesicants (sulfur mustard [HD] and arsenical Lewisite [L]) are agents that generate irritation, blistering, and vesication of the skin, mucous membranes, and lungs. Due to the low volatility, it is considered a persistent chemical agent. HD is an alkylating agent and the alkylation of DNA results in strand breaks, triggering activation of a nuclear DNA repair enzyme, PADPRP. Extreme activity of PADPRP depletes NAD + , a critical cofactor and substrate in glycolysis. This leads to a buildup of glucose‐6‐phosphate, which activates proteases that cleave adherent fibrils connecting the basal epidermal cell layer to the basement membrane. Epithelial cell migration is modulated by cytokines, such as hepatocyte growth factor (HGF), a disulfide‐linked heterodimer (90kDa). We have studied the effects of HGF on the CEES (1/2 mustard surrogate) exposed wounds on Calu‐3 (model of lung epithelial) and keratinocytes (skin) cell lines. The two cell lines were plated on tissue culture inserts and transwells to 80% confluency. The cells were wounded with sterile pipet tips. The wound healing of untreated cells and CEES exposed cells were followed by phase contrast microscopy over 8 days post‐exposure. HGF was added 45 minutes after CEES exposure, and wound repair was also followed for 8 days post‐exposure. HGF enhanced wound healing of both Calu‐3 and keratinocytes, and also wounded cells subsequently exposed to CEES. The % wound closure compared to control, CEES, CEES + HGF was 45%, 36%, and 55% for Calu‐3 cells respectively, and −3% and 36% for CEES and CEES + HGF on keratinocytes. Notably, HGF also decreased CEES induced cell death in both cell lines, although HGF was more potent for Calu‐3 cells. HGF enhanced wound healing and decreased cell death in CEES exposed wounds.