Exposure of human epidermal keratinocyte cell cultures to sulfur mustard promotes binding of complement C1q: Implications for toxicity and medical countermeasures

Sulfur mustard (HD)-increased proteolytic activity, HD-enhanced expression of Pc receptor (FcR) on human epidermal keratinocytes (HEK) and associated inflammatory responses may contribute to HD pathology. Like the FcR, the fi rst component of the classical complement (C') cascade, C1q, binds to the r e region of antibody to mediate inflammatory responses. Complement C1q bind s specifically to the C1q receptor (C1qR) on the blebs of apoptotic human k eratinocytes and is proposed as a cell surface marker for apoptosis, Assays by fluorescent antibodies demonstrated significantly enhanced binding of C 1q to HEK cell cultures exposed to HD, The cell populations of HEK that sho wed enhanced C1q binding also demonstrated an intermediate uptake of propid ium iodide that was greater than in viable unexposed cells but less than in dead cells. The HD-enhanced C1q binding was concentration-dependent, negat ive hy flow cytometry or weakly positive by digital scanning microscopy at 100 muM and positive by both methods at 300 muM Binding of C1q was also tim e-dependent, weakly positive at 8 h, and positive at 16 and 24 h after HD e xposure. The HD-increased C1qR that binds C1q to the surface of HEK might b e a contributing mechanism or a marker for the inflammation and vesication associated with HD exposure.