Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients?
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 neutr...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-07-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01739/full |
id |
doaj-98542d1dea7d4c6eb3abfe28725d319e |
---|---|
record_format |
Article |
spelling |
doaj-98542d1dea7d4c6eb3abfe28725d319e2020-11-25T01:11:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01739471813Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients?Gouri P. Hule0Umair Ahmed Bargir1Manasi Kulkarni2Priyanka Kambli3Prasad Taur4Mukesh Desai5Manisha Rajan Madkaikar6Department of Paediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Paediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Paediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Paediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaBai Jerbai Wadia Hospital for Children, Mumbai, IndiaBai Jerbai Wadia Hospital for Children, Mumbai, IndiaDepartment of Paediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaNicotinamide 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01739/fullperoxisome proliferator-activated receptor gamma agonistspioglitazonechronic granulomatous diseaseneutrophil extracellular trapsreactive oxygen speciesmitochondrial ROS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gouri P. Hule Umair Ahmed Bargir Manasi Kulkarni Priyanka Kambli Prasad Taur Mukesh Desai Manisha Rajan Madkaikar |
spellingShingle |
Gouri P. Hule Umair Ahmed Bargir Manasi Kulkarni Priyanka Kambli Prasad Taur Mukesh Desai Manisha Rajan Madkaikar Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? Frontiers in Immunology peroxisome proliferator-activated receptor gamma agonists pioglitazone chronic granulomatous disease neutrophil extracellular traps reactive oxygen species mitochondrial ROS |
author_facet |
Gouri P. Hule Umair Ahmed Bargir Manasi Kulkarni Priyanka Kambli Prasad Taur Mukesh Desai Manisha Rajan Madkaikar |
author_sort |
Gouri P. Hule |
title |
Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? |
title_short |
Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? |
title_full |
Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? |
title_fullStr |
Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? |
title_full_unstemmed |
Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients? |
title_sort |
does pioglitazone lead to neutrophil extracellular traps formation in chronic granulomatous disease patients? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-07-01 |
description |
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. |
topic |
peroxisome proliferator-activated receptor gamma agonists pioglitazone chronic granulomatous disease neutrophil extracellular traps reactive oxygen species mitochondrial ROS |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01739/full |
work_keys_str_mv |
AT gouriphule doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT umairahmedbargir doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT manasikulkarni doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT priyankakambli doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT prasadtaur doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT mukeshdesai doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients AT manisharajanmadkaikar doespioglitazoneleadtoneutrophilextracellulartrapsformationinchronicgranulomatousdiseasepatients |
_version_ |
1725168957630971904 |