Netting neutrophils in autoimmune small-vessel vasculitis

被引：1305

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

来源：

NATURE MEDICINE | 2009年 / 15卷 / 06期

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

页码：623 / 625

页数：3

共 16 条

[1] Neutrophil extracellular traps kill bacteria [J].

Brinkmann, V ;

Reichard, U ;

Goosmann, C ;

Fauler, B ;

Uhlemann, Y ;

Weiss, DS ;

Weinrauch, Y ;

Zychlinsky, A .

SCIENCE, 2004, 303 (5663) :1532-1535

[2] Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood [J].

Clark, Stephen R. ;

Ma, Adrienne C. ;

Tavener, Samantha A. ;

McDonald, Braedon ;

Goodarzi, Zahra ;

Kelly, Margaret M. ;

Patel, Kamala D. ;

Chakrabarti, Subhadeep ;

McAvoy, Erin ;

Sinclair, Gary D. ;

Keys, Elizabeth M. ;

Allen-Vercoe, Emma ;

DeVinney, Rebekah ;

Doig, Christopher J. ;

Green, Francis H. Y. ;

Kubes, Paul .

NATURE MEDICINE, 2007, 13 (04) :463-469

[3] ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES INDUCE NEUTROPHILS TO DEGRANULATE AND PRODUCE OXYGEN RADICALS INVITRO [J].

FALK, RJ ;

TERRELL, RS ;

CHARLES, LA ;

JENNETTE, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (11) :4115-4119

[4] Novel cell death program leads to neutrophil extracellular traps [J].

Fuchs, Tobias A. ;

Abed, Ulrike ;

Goosmann, Christian ;

Hurwitz, Robert ;

Schulze, Ilka ;

Wahn, Volker ;

Weinrauch, Yvette ;

Brinkmann, Volker ;

Zychlinsky, Arturo .

JOURNAL OF CELL BIOLOGY, 2007, 176 (02) :231-241

[5] Antineutrophil cytoplasmic antibodies induce reactive oxygen-dependent dysregulation of primed neutrophil apoptosis and clearance by macrophages [J].

Harper, L ;

Ren, Y ;

Savill, J ;

Adu, D ;

Savage, COS .

AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (01) :211-220

[6] Nudeosomal DNA fragments in autoimmune diseases [J].

Holdenrieder, Stefan ;

Eichhorn, Peter ;

Beuers, Ulrich ;

Samtleben, Walter ;

Schoenermarck, Ulf ;

Zachoval, Reinhart ;

Nagel, Dorothea ;

Stieber, Petra .

CIRCULATING NUCLEIC ACIDS IN PLASMA AND SERUM IV, 2006, 1075 :318-327

[7] Small-vessel vasculitis [J].

Jennette, JC ;

Falk, RJ .

NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (21) :1512-1523

[8] Mechanisms of Disease: pathogenesis and treatment of ANCA-associated vasculitides [J].

Kallenberg, Cees G. M. ;

Heeringa, Peter ;

Stegeman, Coen A. .

NATURE CLINICAL PRACTICE RHEUMATOLOGY, 2006, 2 (12) :661-670

[9] Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide [J].

Lande, Roberto ;

Gregorio, Josh ;

Facchinetti, Valeria ;

Chatterjee, Bithi ;

Wang, Yi-Hong ;

Homey, Bernhard ;

Cao, Wei ;

Wang, Yui-Hsi ;

Su, Bing ;

Nestle, Frank O. ;

Zal, Tomasz ;

Mellman, Ira ;

Schroeder, Jens-Michael ;

Liu, Yong-Jun ;

Gilliet, Michel .

NATURE, 2007, 449 (7162) :564-U6

[10] Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors [J].

Leadbetter, EA ;

Rifkin, IR ;

Hohlbaum, AM ;

Beaudette, BC ;

Shlomchik, MJ ;

Marshak-Rothstein, A .

NATURE, 2002, 416 (6881) :603-607

← 1 2 →