RESUMO
Antibodies to double stranded (ds) DNA correlate with clinical evolution in systemic lupus erythematosus (SLE) although little is known about the immunogen and target for these antibodies, since ds DNA is poorly immunogenic. We now show that monoclonal anti DNA antibodies similar to those detected in human SLE can be produced by immunization of genetically non-autoimmune mice with a human circulating DNA-protein complex increased in the circulation of SLE patients. One such monoclonal antibody showed antinuclear reactivity, interacting with a 74 kd DNA-binding membrane protein, in reactions prevented by absorption with ds DNA cellulose. Our data suggests that anti ds DNA antibody reactions in SLE may be triggered by circulating nucleoproteins and directed toward membrane receptors capable of interacting with extracellular DNA.
Assuntos
Anticorpos Antinucleares/imunologia , Desoxirribonucleoproteínas/sangue , Lúpus Eritematoso Sistêmico/sangue , Anticorpos Monoclonais , Linhagem Celular , Membrana Celular/metabolismo , DNA/imunologia , Desoxirribonucleoproteínas/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Placenta/metabolismo , GravidezRESUMO
By means of controlled mechanical shearing it was possible to fractionate human breast tumor chromatin in "active" and "inactive" species, according to their in vitro template activity, using Escherichia coli RNA polymerase. The "active" molecules can be resolved in three well defined regions in an exponential sucrose gradient, showing approximately 300 times the efficiency for synthesizing ribonucleic acid, relative to the chromatin which migrated fastest. This technique could provide the initial tool to isolate eu-and heterochromatin from native human chromatin.