Sulfur mustard exposure enhances Fc receptor expression on human epidermal keratinocytes in cell culture: implications for toxicity and medical countermeasures.
Sulfur mustard (HD) is a chemical warfare blister agent. The biochemical basis of HD-induced vesication is unknown, and no antidote currently exists. Basal epidermal cells are a major site of HD toxicity in vivo, with inflammation and HD-increased proteolytic activity implicated as factors that contribute to HD pathology. Fc receptors (FcR) bind to the Fc region of antibody to mediate many effector and regulatory functions that can influence inflammatory responses. FcR are found on all types of immune cells and are also expressed on the surface of human keratinocytes. Assay by fluorescent antibodies demonstrated significantly enhanced CD32 (FcRII) and CD16 (FcRIII) on human epidermal keratinocyte (HEK) cell cultures at 8 to 24 h after exposure to HD (50, 100 and 200 micromol/L). The enhanced CD32 was time- and concentration-dependent and agreed well with the time course of increased proteolysis and cutaneous pathology observed during HD vesication. HD-increased FcR on the surface of HEK might be a mechanism of vesication.
Cowan
F M
FM
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425, USA.
Broomfield
C A
CA
Smith
W J
WJ
D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D017452:Receptors, IgG / Q000096:biosynthesis*
D002619:Chemical Warfare Agents; D017452:Receptors, IgG; D009151:Mustard Gas