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Eur J Immunol. 2016 Jan;46(1):178-84. doi: 10.1002/eji.201545615. Epub 2015 Dec 2.

NET formation can occur independently of RIPK3 and MLKL signaling.

Author information

1
Institute of Pharmacology, University of Bern, Bern, Switzerland.
2
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

Abstract

The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor-interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3-deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently of both RIPK3 and MLKL signaling.

KEYWORDS:

MLKL; NET formation; NETosis; Necroptosis; Neutrophils; RIPK

PMID:
26549703
PMCID:
PMC4738457
DOI:
10.1002/eji.201545615
[Indexed for MEDLINE]
Free PMC Article

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