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Published on: October 23, 2017
Two-in-one: UV radiation simultaneously induces apoptosis and NETosis
Dhia Azzouz1,2, Meraj A Khan1,2, Neil Sweezey1,3,4
11Program in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON Canada.
Ultraviolet (UV) irradiation can induce both neutrophil extracellular trap formation (NETosis) and apoptosis simultaneously. This study identifies a novel form of NOX-independent NETosis, termed "ApoNETosis", triggered by UV exposure.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- NETosis is a distinct form of programmed cell death in neutrophils.
- The potential for simultaneous NETosis and apoptosis in a single neutrophil remains unclear.
Purpose of the Study:
- To investigate whether neutrophils can undergo both NETosis and apoptosis concurrently.
- To characterize the mechanisms of UV-induced NETosis.
Main Methods:
- Neutrophils were exposed to increasing doses of ultraviolet (UV) irradiation.
- NETosis was assessed by myeloperoxidase (MPO) colocalization to extracellular DNA.
- Caspase 3 activation, mitochondrial ROS generation, and p38/ERK phosphorylation were measured.
- Inhibitors of ROS production, p38, and NADPH oxidase (NOX) were used.
- Transcriptional activity and cell death pathways were analyzed.
Main Results:
- UV irradiation dose-dependently increased NETosis and caspase 3 activation.
- UV-induced NETosis was dependent on mitochondrial ROS and p38 activation, but independent of NOX activity.
- UV-induced NETosis required transcriptional firing for chromatin decondensation.
- UV-mediated NETosis was distinct from apoptosis, necrosis, and necroptosis.
Conclusions:
- Increasing UV doses induce simultaneous apoptosis and NETosis in neutrophils.
- UV triggers a novel form of NOX-independent NETosis, designated "ApoNETosis".
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