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 Fc receptor (FcR) on human epidermal keratinocytes (HEK) and associated inflammatory responses may contribute to HD pathology. Like the FcR, the first component of the classical complement (C') cascade, C1q, binds to the Fc region of antibody to mediate inflammatory responses. Complement C1q binds specifically to the C1q receptor (C1qR) on the blebs of apoptotic human keratinocytes and is proposed as a cell surface marker for apoptosis. Assays by fluorescent antibodies demonstrated significantly enhanced binding of C1q to HEK cell cultures exposed to HD. The cell populations of HEK that showed enhanced C1q binding also demonstrated an intermediate uptake of propidium iodide that was greater than in viable unexposed cells but less than in dead cells. The HD-enhanced C1q binding was concentration-dependent, negative by flow cytometry or weakly positive by digital scanning microscopy at 100 microM and positive by both methods at 300 microM. Binding of C1q was also time-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 vesication associated with HD exposure.
Cowan
F M
FM
Biochemical Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Broomfield
C A
CA
Smith
W J
WJ
D000954:Antigens, Surface; D017209:Apoptosis; D001665:Binding Sites; D001768:Blister / Q000139:chemically induced / Q000503:physiopathology; D002352:Carrier Proteins; D018929:Cell Culture Techniques; D015922:Complement C1q / Q000378:metabolism*; D003879:Dermatologic Agents / Q000633:toxicity*; D006801:Humans; D018960:Hyaluronan Receptors; D007249:Inflammation; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009151:Mustard Gas / Q000633:toxicity*; D011951:Receptors, Complement / Q000502:physiology*; D011961:Receptors, Fc / Q000096:biosynthesis*
D000954:Antigens, Surface; C087299:C1QBP protein, human; D002352:Carrier Proteins; D003879:Dermatologic Agents; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D011961:Receptors, Fc; C032402:complement 1q receptor; D015922:Complement C1q; D009151:Mustard Gas