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PMA and crystal‐induced neutrophil extracellular trap formation involves RIPK1‐RIPK3‐MLKL signaling

Desai, Jyaysi, Kumar, Santhosh V., Mulay, Shrikant R., Konrad, Lukas, Romoli, Simone, Schauer, Christine, Herrmann, Martin, Bilyy, Rostyslav, Müller, Susanna, Popper, Bastian, Nakazawa, Daigo, Weidenbusch, Marc, Thomasova, Dana, Krautwald, Stefan, Linkermann, Andreas, Anders, Hans‐Joachim·2016·European Journal of Immunology

Abstract

Neutrophil extracellular trap (NET) formation contributes to gout, autoimmune vasculitis, thrombosis, and atherosclerosis. The outside‐in signaling pathway triggering NET formation is unknown. Here, we show that the receptor‐interacting protein kinase (RIPK)‐1‐stabilizers necrostatin‐1 or necrostatin‐1s and the mixed lineage kinase domain‐like (MLKL)‐inhibitor necrosulfonamide prevent monosodium urate (MSU) crystal‐ or PMA‐induced NET formation in human and mouse neutrophils. These compounds do not affect PMA‐ or urate crystal‐induced production of ROS. Moreover, neutrophils of chronic granulomatous disease patients are shown to lack PMA‐induced MLKL phosphorylation. Genetic deficiency of RIPK3 in mice prevents MSU crystal‐induced NET formation in vitro and in vivo. Thus, neutrophil death and NET formation may involve the signaling pathway defining necroptosis downstream of ROS production. These data imply that RIPK1, RIPK3, and MLKL could represent molecular targets in gout or other crystallopathies.

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Metadata

Authors
Desai, J., Kumar, S. V., Mulay, S. R., Konrad, L., Romoli, S., Schauer, C., Herrmann, M., Bilyy, R., Müller, S., Popper, B., Nakazawa, D., Weidenbusch, M., Thomasova, D., Krautwald, S., Linkermann, A., & Anders, H.
Venue
European Journal of Immunology
Publisher
Wiley
Published
2015-11-30
Volume
46
Issue
1
Pages
223-229
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
OpenAlex
W2254713269
Cited by
233
References
9
FWCI
10.31
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: PMA and crystal‐induced neutrophil extracellular trap formation involves RIPK1‐RIPK3‐MLKL signaling. https://app.cochat.ai/papers/10.1002/eji.201545605
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Desai, J., Kumar, S. V., Mulay, S. R., Konrad, L., Romoli, S., Schauer, C., Herrmann, M., Bilyy, R., Müller, S., Popper, B., Nakazawa, D., Weidenbusch, M., Thomasova, D., Krautwald, S., Linkermann, A., & Anders, H. (2016). PMA and crystal‐induced neutrophil extracellular trap formation involves RIPK1‐RIPK3‐MLKL signaling. European Journal of Immunology. https://doi.org/10.1002/eji.201545605

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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