Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IgG anti-double stranded DNA antibodies (anti-dsDNA) purified from serum of patients with active systemic lupus erythematosus (SLE), have been found to be cytotoxic to the cultured rat mesangial cells (MC). In the present study, by use of immunofluorescent staining, immunoblotting, radioimmunoprecipitation, and cell cycle analysis, we showed that IgG anti-dsDNA could bind to the membrane of MC. The bound epitope was a 28 kDa protein, which would disappear if the cells were treated in advance with proteinase K (100 micrograms/ml). In addition, binding of MC by 20 micrograms/ml of anti-dsDNA IgG F(ab')2 activated plasma membrane (equivalent to 80 IU/ml of calf thymus double-stranded DNA binding activity) resulted in release of much more 3H-arachidonic acid than binding by 20 micrograms/ml of human IgG F(ab')2 (26.71 +/- 3.75% in the case of anti-dsDNA vs. 4.73 +/- 2.86% in the case of IgG). To understand further the cytotoxic mechanism of anti-dsDNA, we incubated MC with anti-dsDNA, for a variety of periods (from 10 minutes to 24 hours). After incubation, the cells were fixed and stained with hematoxylin-eosin for morphologic observation. Simultaneously, the genomic DNA was extracted and analyzed in 1.8% agarose gel electrophoresis. We found that cell death caused anti-dsDNA followed a process of apoptosis rather than necrosis. These results suggest that binding of anti-dsDNA with MC membrane may activate endonuclease which will fracture the DNA and lead to programmed cell death.
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PMID:Polyclonal IgG anti-dsDNA antibodies exert cytotoxic effect on cultured rat mesangial cells by binding to cell membrane and augmenting apoptosis. 835 8

Nucleosomes are major autoantigens in systemic lupus erythematosus. These are found as circulating complexes in both lupus patients and lupus mice. The existence of a potential ubiquitous cell surface receptor specific for nucleosomes has been suggested. However, neither the nature nor the role of this receptor has been identified. Moreover, the consequence of receptor-nucleosome interaction on the target cell has not been studied in detail so far. We show here that purified nucleosomes induce cell death of normal and lupus lymphocytes ex vivo in a dose- and time-dependent manner whereas human dendritic cells were relatively resistant. Most importantly, nucleosome-induced cell death is primary necrosis. Moreover, necrosis could be abolished when nucleosomes were first treated with deoxyribonuclease I, proteinase K or with a specific monoclonal antibody. Finally, intravenous injections of purified nucleosomes result in a reduced spleen cell number compared to buffer-injected mice, indicating that circulating nucleosomes may behave similarly in vivo. Taken together, this is the first report indicating that nucleosomes are able to induce necrosis,which in turn could result in an amplification loop of the disease causing the inflammation observed in lupus patients.
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PMID:Nucleosomes induce lymphocyte necrosis. 1288 64