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

Text Simon_Necroptosis_Neutro_JI2016Suppl (003).pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (2MB) | Request a copy

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.

Interest & Impact

Downloads

3 since deposited on 29 Dec 2016
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item