Anti-DNA autoantibodies reveal toxicity to tumor cell lines.
Cytotoxicity of anti-DNA autoantibodies from sera of SLE and CLL patients was assayed on permanent cell lines L929, HL-60, Raji, and K562. L929 cells appeared to be the most sensitive to antibody treatment. DNA-hydrolyzing properties of the same autoantibody preparations were analyzed in parallel. The data obtained outlined the correlation between cytotoxicity and DNA-hydrolyzing properties of these autoantibodies. It was shown that treatment of the cells with cytotoxic anti-DNA autoantibodies induced internucleosomal DNA fragmentation and Annexin V binding to the cell surface characteristic of apoptotic pathway of cell death. A time-dependent profile of antibody-mediated toxicity to L929 cells suggested recruitment of at least two distinct mechanisms of cell death. The first peak of cell death observed in 3 h of incubation was completely inhibited by preincubation of cells with caspase inhibitor YVAD-CHO, while the second increase in cell mortality (18-30 h) persisted. Possible mechanisms for anti-DNA autoantibody cytotoxicity are discussed.
Kozyr
A V
AV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya st., 16/10, Moscow, Russia.
Sashchenko
L P
LP
Kolesnikov
A V
AV
Zelenova
N A
NA
Khaidukov
S V
SV
Ignatova
A N
AN
Bobik
T V
TV
Gabibov
A G
AG
Alekberova
Z S
ZS
Suchkov
S V
SV
Gnuchev
N V
NV
D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000633:toxicity*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007106:Immune Sera / Q000276:immunology / Q000633:toxicity; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000633:toxicity; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D061945:Caspase Inhibitors; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D004247:DNA; D020169:Caspases