Exposure of human epidermal keratinocyte cell cultures to sulfur mustard promotes binding of complement C1q: Implications for toxicity and medical countermeasures
Fm. Cowan et al., Exposure of human epidermal keratinocyte cell cultures to sulfur mustard promotes binding of complement C1q: Implications for toxicity and medical countermeasures, J APPL TOX, 21, 2000, pp. S77-S80
Sulfur mustard (HD)-increased proteolytic activity, HD-enhanced expression
of Fc 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
Pc region of antibody to mediate inflammatory responses. Complement C1q bin
ds specifically to the C1q receptor (C1qR) on the blebs of apoptotic human
keratinocytes and is proposed as a cell surface marker for apoptosis, Assay
s by fluorescent antibodies demonstrated significantly enhanced binding of
C1q to HEK cell cultures exposed to HD, The cell populations of HEK that sh
owed enhanced C1q binding also demonstrated an intermediate uptake of propi
dium iodide that was greater than in viable unexposed cells but less than i
n dead cells. The HD-enhanced C1q binding was concentration-dependent, nega
tive by 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 t
ime-dependent, weakly positive at 8 h, and positive at 16 and 24 h after HD
exposure. The HD-increased C1qR that binds C1q to the surface of HEK might
be a contributing mechanism or a marker for the inflammation and vesicatio
n associated with no exposure. Published in 2000 by John Wiley & Sons, Ltd.