Systemic lupus-erythematosus: deoxyribonuclease 1 in necrotic chromatin disposal.
Systemic lupus-erythematosus is an auto-immune-disease characterized by pathogenic anti-nuclear auto-antibodies. These form immune-complexes that after deposition at basal membranes at various locations initiate inflammatory reactions. There is a clear genetic and gender predisposition (females are affected 10 times more frequently), but also infectious agents and further environmental factors have been shown to be causative for the initiation of the disease. It has been suggested that the auto-antibodies arise after release and/or inefficient removal of nuclear components during cell death (defective cellular "waste disposal" theory). So far, increased apoptotic cell death has been made responsible, but recent data suggest that defective cellular waste disposal during/after necrosis may also lead to the release and prolonged exposure of nuclear components. Here, we concentrate on chromatin disposal during necrosis and the involvement of Deoxyribonuclease 1 in this process with respect to its possible role in the prevention of anti-nuclear auto-immunity.
Napirei
Markus
M
Abteilung für Anatomie und Embryologie, Medizinische Fakultät, Ruhr-Universität, Bochum, Germany.
Gültekin
Aykut
A
Kloeckl
Thomas
T
Möröy
Tarik
T
Frostegård
Johan
J
Mannherz
Hans Georg
HG
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000974:Antibodies, Antinuclear; D002843:Chromatin; D011993:Recombinant Fusion Proteins; D003850:Deoxyribonuclease I