Neutrophil Necroptosis Is Triggered by Ligation of Adhesion Molecules following GM-CSF Priming.

Wang, Xiaoliang; Simon, Hans-Uwe; He, Zhaoyue; Liu, He; Yousefi, Shida (2016). Neutrophil Necroptosis Is Triggered by Ligation of Adhesion Molecules following GM-CSF Priming. Journal of immunology, 197(10), pp. 4090-4100. American Association of Immunologists 10.4049/jimmunol.1600051

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Apoptosis is the most common form of neutrophil death under both physiological and inflammatory conditions. However, forms of nonapoptotic neutrophil death have also been observed. In the current study, we report that human neutrophils undergo necroptosis after exposure to GM-CSF followed by the ligation of adhesion receptors such as CD44, CD11b, CD18, or CD15. Using a pharmacological approach, we demonstrate the presence of a receptor-interacting protein kinase-3 (RIPK3)-a mixed lineage kinase-like (MLKL) signaling pathway in neutrophils which, following these treatments, first activates p38 MAPK and PI3K, that finally leads to the production of high levels of reactive oxygen species (ROS). All these steps are required for necroptosis to occur. Moreover, we show that MLKL undergoes phosphorylation in neutrophils in vivo under inflammatory conditions. This newly identified necrosis pathway in neutrophils would imply that targeting adhesion molecules could be beneficial for preventing exacerbation of disease in the neutrophilic inflammatory response.

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:

Simon, Hans-Uwe; He, Zhaoyue; Liu, He and Yousefi, Shida

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Jana Berger

Date Deposited:

29 Dec 2016 11:12

Last Modified:

13 Sep 2017 15:39

Publisher DOI:

10.4049/jimmunol.1600051

PubMed ID:

27815445

BORIS DOI:

10.7892/boris.90777

URI:

https://boris.unibe.ch/id/eprint/90777

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