Netting neutrophils in autoimmune small-vessel vasculitis

被引:1274
|
作者
Kessenbrock, Kai [1 ,2 ]
Krumbholz, Markus [1 ,3 ]
Schoenermarck, Ulf [4 ]
Back, Walter [5 ]
Gross, Wolfgang L. [6 ,7 ]
Werb, Zena [2 ]
Groene, Hermann-Josef [8 ]
Brinkmann, Volker [9 ]
Jenne, Dieter E. [1 ]
机构
[1] Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany
[2] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[3] Univ Munich, Inst Clin Neuroimmunol, Munich, Germany
[4] Univ Hosp Grosshadern, Med Clin 1, Div Nephrol, Munich, Germany
[5] Univ Heidelberg, Mannheim Clin, Dept Pathol, D-6800 Mannheim, Germany
[6] Med Univ Lubeck, Univ Klinikum Schleswig Holstein, Vasculitis Ctr, Dept Rheumatol, D-23538 Lubeck, Germany
[7] Rheumaklin Bad Bramstedt, Lubeck, Germany
[8] German Canc Res Ctr, Dept Cellular & Mol Pathol, D-6900 Heidelberg, Germany
[9] Max Planck Inst Infect Biol, Microscopy Core Facil, Berlin, Germany
基金
美国国家卫生研究院;
关键词
ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES; EXTRACELLULAR TRAPS; DNA; MYELOPEROXIDASE; CELLS;
D O I
10.1038/nm.1959
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.
引用
收藏
页码:623 / 625
页数:3
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