Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages

摘要: A large amount of chromosomal DNA is degraded during programmed cell death and definitive erythropoiesis. DNase II an enzyme that digests the apoptotic cells nuclei expelled from erythroid precursor after macrophages have engulfed them. Here we show II-/-IFN-IR-/- mice with induced deletion gene develop a chronic polyarthritis resembling human rheumatoid arthritis. set cytokine genes was strongly activated in affected joints these mice, their serum contained high levels anti-cyclic citrullinated peptide antibody, factor matrix metalloproteinase-3. Early pathogenesis, expression encoding tumour necrosis (TNF)-alpha upregulated bone marrow, administration anti-TNF-alpha antibody prevented development These results indicate if cannot degrade mammalian precursors cells, they produce TNF-alpha, which activates synovial to various cytokines, leading polyarthritis.