Mouse monoclonal autoantibodies penetrate mouse macrophage cells and stimulate NF-kappaB activation and TNF-alpha release.
Autoantibodies against double-stranded DNA (dsDNA) are found in the serum of systemic lupus erythematosus (SLE) patients. However, the mechanism by which anti-dsDNA antibodies (Abs) contribute to the pathogenesis of SLE is not yet fully understood. In this study, we investigated four anti-dsDNA mouse monoclonal autoantibodies that share positively charged amino acids (including arginines) in their complementarity determining regions for their ability to penetrate RAW264.7 macrophage cells, activate NF-kappaB and stimulate TNF-alpha production. All four antibodies penetrated into macrophage cells and increased the level of extracellular TNF-alpha; two also activated NF-kappaB. The fact that two of four cell-penetrating anti-dsDNA mAbs induced both NF-kappaB activation and TNF-alpha production in macrophages suggests that at least some autoantibodies against dsDNA may play a role in the pathogenesis of SLE by penetrating into macrophage cells and nuclei, and subsequently inducing the pro-inflammatory cytokine, TNF-alpha, by binding to the NF-kappaB gene and stimulating its transcriptional activity.
Jang
Eun-Jung
EJ
Institute for Medical Science and Brain Korea 21 Program, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
Nahm
Dong-Ho
DH
Jang
Young-Ju
YJ
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004247:DNA