NET formation can occur independently of RIPK3 and MLKL signaling

Amini, Poorya; Stojkov, Darko; Wang, Xiaoliang; Wicki, Simone; Kaufmann, Thomas; Wong, Wendy Wei-Lynn; Simon, Hans-Uwe; Yousefi, Shida (2016). NET formation can occur independently of RIPK3 and MLKL signaling. European journal of immunology, 46(1), pp. 178-184. Wiley-VCH 10.1002/eji.201545615

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Amini, Poorya; Stojkov, Darko; Wang, Xiaoliang; Wicki, Simone; Kaufmann, Thomas; Simon, Hans-Uwe and Yousefi, Shida

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

José Schranz

Date Deposited:

03 Feb 2016 13:13

Last Modified:

03 Feb 2016 13:13

Publisher DOI:

10.1002/eji.201545615

PubMed ID:

26549703

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.76220

URI:

https://boris.unibe.ch/id/eprint/76220

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