Defective nuclear entry of hydrolases prevents neutrophil extracellular trap formation in patients with chronic granulomatous disease

[...]in all of these studies, no direct correlation of macroautophagic activity and NETosis could be reported, and only pharmacologic inhibition of phosphatidylinositol 3 (PI3)-kinase activity was used to compromise macroautophagy. [...]we decided to revisit the regulation of macroautophagy and ROS...

Full description

Saved in:
Bibliographic Details
Published in:Journal of allergy and clinical immunology 2015-12, Vol.136 (6), p.1703-1706.e5
Main Authors: Romao, Susana, PhD, Puente, Emilio Tejera, PhD, Nytko, Katarzyna J., PhD, Siler, Ulrich, PhD, Münz, Christian, PhD, Reichenbach, Janine, MD
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - pharmacology
Allergy and Immunology
Androstadienes - pharmacology
Benzylamines - pharmacology
Candida albicans
Cell Nucleus - immunology
Cell Nucleus - metabolism
Deoxyribonucleic acid
DNA
Extracellular Traps
Granulomatous Disease, Chronic - immunology
Granulomatous Disease, Chronic - metabolism
Histones - metabolism
Humans
Hydrolases - immunology
Immunoglobulins
Kinases
Localization
Membranes
Microscopy
Neutrophils
Neutrophils - drug effects
Neutrophils - immunology
Neutrophils - metabolism
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - immunology
Quinazolines - pharmacology
Reactive Oxygen Species - immunology
Studies
Tetradecanoylphorbol Acetate - pharmacology
Wortmannin
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[...]in all of these studies, no direct correlation of macroautophagic activity and NETosis could be reported, and only pharmacologic inhibition of phosphatidylinositol 3 (PI3)-kinase activity was used to compromise macroautophagy. [...]we decided to revisit the regulation of macroautophagy and ROS production by PI3-kinase inhibition during NETosis in neutrophils from patients with CGD and healthy donors (HDs). [...]the PI3-kinase inhibitor 3-MA and, to a lesser extent, other PI3-kinase inhibitors, such as wortmannin and spautin-1, can inhibit NETosis. Because 3-MA is classically used as a macroautophagy inhibitor, we investigated accumulation of autophagosomes in neutrophils treated with opsonized yeast and PMA with or without 3-MA through immunofluorescent quantification of dots positive for light chain 3B (LC3B), which becomes attached to autophagosome membranes.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2015.09.007