Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients?

Autor: Umair Ahmed Bargir, Manasi Kulkarni, Priyanka Kambli, Gouri Hule, Mukesh Desai, Prasad Taur, Manisha Madkaikar
Rok vydání: 2019
Předmět:
lcsh:Immunologic diseases. Allergy
Male
0301 basic medicine
Mitochondrial ROS
Enzyme complex
Neutrophils
Immunology
neutrophil extracellular traps
chronic granulomatous disease
mitochondrial ROS
Mitochondrion
Pharmacology
Granulomatous Disease
Chronic
MitoSOX red
Extracellular Traps
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Chronic granulomatous disease
medicine
Humans
Immunology and Allergy
Child
NOX independnent NETosis
Original Research
reactive oxygen species
NADPH oxidase
Pioglitazone
biology
Superoxide
Infant
NADPH Oxidases
Neutrophil extracellular traps
medicine.disease
Mitochondria
PPAR gamma
030104 developmental biology
chemistry
Child
Preschool
biology.protein
peroxisome proliferator-activated receptor gamma agonists
Female
lcsh:RC581-607
030215 immunology
medicine.drug
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Vol 10 (2019)
ISSN: 1664-3224
Popis: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme complex responsible for reactive oxygen species (ROS) production, is defective in chronic granulomatous disease (CGD) patients. This enzyme helps in antimicrobial host defense by phagocytes. CGD patients are unable to form neutrophil extracellular traps (NETs), which are composed of granule-derived proteins from neutrophils decorated with decondensed chromatin. Mitochondria have gained attention, being a rich source of flavochrome enzymes due to the presence of several sites for superoxide production. Recently, PPARγ agonists, a mitochondrial ROS inducer, induce mitochondrial ROS formation post-treatment in murine NADPH oxidase knockout models. Mitochondrial ROS is also essential for NOX-independent NETosis. Our study for the first time detects induction of NETosis independent of NADPH oxidase post-treatment with agonists such as pioglitazone and rosiglitazone in CGD subjects. Neutrophils isolated from CGD subjects were treated with pioglitazone and rosiglitazone. After treatment, qualitative analysis of NET formation was done using confocal microscopy after staining with DAPI. Quantitative estimation of extracellular DNA was performed using Sytox green. Mitochondrial ROS production with PPARγ agonist-treated/untreated neutrophils was detected using MitoSOX red. Pioglitazone and rosiglitazone induce significant NET formation in CGD patients. Our data clearly signify the effect of PPARγ agonists in induction of NET formation in CGD cases. Apart from the proposed experimental studies regarding the detailed mechanism of action, controlled trials could provide valuable information regarding the clinical use of pioglitazone in CGD patients as curative HSCT remains challenging in developing countries.
Databáze: OpenAIRE
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