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Exposure of human epidermal keratinocyte cell cultures to sulfur mustard promotes binding of complement C1q: implications for toxicity and medical countermeasures † ‡
Author(s) -
Cowan Fred M.,
Broomfield Clarence A.,
Smith William J.
Publication year - 2000
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/1099-1263(200012)20:1+<::aid-jat686>3.0.co;2-e
Subject(s) - flow cytometry , propidium iodide , hek 293 cells , apoptosis , antibody , complement system , sulfur mustard , receptor , microbiology and biotechnology , cell culture , biology , inflammation , chemistry , keratinocyte , cell , toxicity , programmed cell death , immunology , biochemistry , genetics , organic chemistry
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 μM and positive by both methods at 300 μM. 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. Published in 2000 by John Wiley & Sons, Ltd.