Two-in-one: UV radiation simultaneously induces apoptosis and NETosis

Dhia Azzouz; Meraj A Khan; Neil Sweezey; Nades Palaniyar

doi:10.1038/s41420-018-0048-3

Two-in-one: UV radiation simultaneously induces apoptosis and NETosis

Cell Death Discov. 2018 Apr 27:4:51. doi: 10.1038/s41420-018-0048-3. eCollection 2018.

Authors

Dhia Azzouz^{1

2}, Meraj A Khan^{1

2}, Neil Sweezey^{1

3

4}, Nades Palaniyar^{1

2

4

5}

Affiliations

¹ 1Program in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON Canada.
² 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada.
³ 3Department of Paediatrics and Physiology, University of Toronto, Toronto, ON Canada.
⁴ 4Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON Canada.
⁵ 5Massachusetts General Hospital and Shriners Hospitals for Children in Boston, Harvard Medical School, Boston, MA USA.

Abstract

NETosis is a unique form of neutrophil death that differs from apoptosis and necrosis. However, whether NETosis and apoptosis can occur simultaneously in the same neutrophil is unknown. In this paper, we show that increasing doses of ultraviolet (UV) irradiation increases NETosis, which is confirmed by myeloperoxidase colocalisation to neutrophil extracellular DNA. Increasing UV irradiation increases caspase 3 activation, mitochondrial reactive oxygen species (ROS) generation and p38, but not ERK, phosphorylation. Inhibition of mitochondrial ROS production and p38 activation, but not NADPH oxidase (NOX) activity, suppresses UV-induced NETosis, indicating that UV induces NOX-independent NETosis. Like classical NOX-dependent and -independent NETosis, UV-induced NETosis requires transcriptional firing for chromatin decondensation. Cell death-specific inhibitor studies indicate that UV-mediated NETosis is not apoptosis, necrosis or necroptosis. Collectively, these studies indicate that increasing doses of UV irradiation induce both apoptosis and NETosis simultaneously, but the ultimate outcome is the induction of a novel form of NOX-independent NETosis, or "ApoNETosis".