Netting neutrophils in autoimmune small-vessel vasculitis

Kai Kessenbrock; Markus Krumbholz; Ulf Schönermarck; Walter Back; Wolfgang L. Gross; Zena Werb; Hermann Josef Gröne; Volker Brinkmann; Dieter E. Jenne

doi:10.1038/nm.1959

Netting neutrophils in autoimmune small-vessel vasculitis

Kai Kessenbrock^*, Markus Krumbholz, Ulf Schönermarck, Walter Back, Wolfgang L. Gross, Zena Werb, Hermann Josef Gröne, Volker Brinkmann, Dieter E. Jenne

^*Corresponding author for this work

Clinic of Rheumatology

1434 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Medicine
Volume	15
Issue number	6
Pages (from-to)	623-625
Number of pages	3
ISSN	1078-8956
DOIs	https://doi.org/10.1038/nm.1959
Publication status	Published - 08.06.2009

Funding

We would like to thank W. Samtleben for providing serum samples, R. Bittner for technical assistance and E. Csernok and A. Kniepert for help with serum samples. Moreover, we are grateful to M. Sixt and E. Meinl for helpful suggestions and H. Wekerle for his constant interest and support of this work. We also thank M. Monestier (Temple University) for providing us with histone-specific monoclonal antibody and G. Koch (University of Freiburg) for the kind gift of the antibody specific for MxA. This work was funded by the Deutsche Forschungsgemeinschaft (SFB 571). It was further supported by the US National Institutes of Health (AI053194) and by fellowships from the Susan G. Komen for the Cure Foundation and the Alexander von Humboldt Foundation.

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nm.1959

Cite this

@article{19b8fb4f46a64b66a8a6283da4d7a887,

title = "Netting neutrophils in autoimmune small-vessel vasculitis",

abstract = "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.",

author = "Kai Kessenbrock and Markus Krumbholz and Ulf Sch{\"o}nermarck and Walter Back and Gross, \{Wolfgang L.\} and Zena Werb and Gr{\"o}ne, \{Hermann Josef\} and Volker Brinkmann and Jenne, \{Dieter E.\}",

year = "2009",

month = jun,

day = "8",

doi = "10.1038/nm.1959",

language = "English",

volume = "15",

pages = "623--625",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "6",

}

TY - JOUR

T1 - Netting neutrophils in autoimmune small-vessel vasculitis

AU - Kessenbrock, Kai

AU - Krumbholz, Markus

AU - Schönermarck, Ulf

AU - Back, Walter

AU - Gross, Wolfgang L.

AU - Werb, Zena

AU - Gröne, Hermann Josef

AU - Brinkmann, Volker

AU - Jenne, Dieter E.

PY - 2009/6/8

Y1 - 2009/6/8

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/67349279881

U2 - 10.1038/nm.1959

DO - 10.1038/nm.1959

M3 - Journal articles

C2 - 19448636

AN - SCOPUS:67349279881

SN - 1078-8956

VL - 15

SP - 623

EP - 625

JO - Nature Medicine

JF - Nature Medicine

IS - 6

ER -

Netting neutrophils in autoimmune small-vessel vasculitis

Abstract

Funding

Research Areas and Centers

UN SDGs

Access to Document

Other files and links

Fingerprint

CRU 170: Early Pathogenesis of Wegener's Granulomatosis: From Innate Immunity with Granuloma Formation to Autoimmunity.

Cite this

Netting neutrophils in autoimmune small-vessel vasculitis

Abstract

Funding

Research Areas and Centers

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRU 170: Early Pathogenesis of Wegener's Granulomatosis: From Innate Immunity with Granuloma Formation to Autoimmunity.

Cite this