Metabolic pathways involved in formation of spontaneous and lipopolysaccharide-induced neutrophil extracellular traps (NETs) differ in obesity and systemic inflammation

2021
journal article
article
15
dc.abstract.enObesity manifests itself with low-grade chronic inflammation that shapes immune responses during infection. Albeit obese individuals are at risk of higher mortality due to comorbidities, they are better protected from systemic inflammation. Recently, we showed that in the vasculature of obese mice kept on high-fat diet (HFD), neutrophils produce less neutrophil extracellular traps (NETs) than in lean controls (normal diet, ND). NETs are used by neutrophils to counteract severe infection, but they also cause collateral damage. Hardly anything is known about metabolic requirements for their formation, especially in the context of obesity and/or sepsis. Thus, we aimed to study the immunometabolism of NET formation by application of ex vivo neutrophil analyses (Seahorse analyzer, selective inhibitors, confocal imaging) and intravital microscopy. The obtained data show that glycolysis and/or pentose phosphate pathway are involved in NETs release by ND neutrophils in both physiological and inflammatory conditions. In contrast, such cells of septic HFD mice utilize these routes only to spontaneously cast NETs, while after secondary ex vivo activation they exhibit so called "exhausted phenotype", which manifests itself in diminished NET release despite high glycolytic potential and flexibility to oxidize fatty acids. Moreover, impact of ATP synthase inhibition on NET formation is revealed. Overall, the study shows that the neutrophil potential to cast NETs depends on both the metabolic and inflammatory state of the individual.pl
dc.affiliationWydział Biologii : Instytut Zoologii i Badań Biomedycznychpl
dc.contributor.authorCichoń, Iwona - 178006 pl
dc.contributor.authorOrtmann, Weronika - 213274 pl
dc.contributor.authorKołaczkowska, Elżbieta - 129011 pl
dc.date.accessioned2021-07-30T10:01:15Z
dc.date.available2021-07-30T10:01:15Z
dc.date.issued2021pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number14pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume22pl
dc.identifier.articleid7718pl
dc.identifier.doi10.3390/ijms22147718pl
dc.identifier.eissn1422-0067pl
dc.identifier.issn1661-6596pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/276625
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeotwarte czasopismo
dc.subject.enimmunometabolismpl
dc.subject.enneutrophil extracellular trapspl
dc.subject.enneutrophilspl
dc.subject.enobesitypl
dc.subject.enGLUT1pl
dc.subject.englycolysispl
dc.subject.enPPP pathwaypl
dc.subject.enfatty acidspl
dc.subject.enATP synthasepl
dc.subject.ensystemic inflammationpl
dc.subtypeArticlepl
dc.titleMetabolic pathways involved in formation of spontaneous and lipopolysaccharide-induced neutrophil extracellular traps (NETs) differ in obesity and systemic inflammationpl
dc.title.journalInternational Journal of Molecular Sciencespl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Obesity manifests itself with low-grade chronic inflammation that shapes immune responses during infection. Albeit obese individuals are at risk of higher mortality due to comorbidities, they are better protected from systemic inflammation. Recently, we showed that in the vasculature of obese mice kept on high-fat diet (HFD), neutrophils produce less neutrophil extracellular traps (NETs) than in lean controls (normal diet, ND). NETs are used by neutrophils to counteract severe infection, but they also cause collateral damage. Hardly anything is known about metabolic requirements for their formation, especially in the context of obesity and/or sepsis. Thus, we aimed to study the immunometabolism of NET formation by application of ex vivo neutrophil analyses (Seahorse analyzer, selective inhibitors, confocal imaging) and intravital microscopy. The obtained data show that glycolysis and/or pentose phosphate pathway are involved in NETs release by ND neutrophils in both physiological and inflammatory conditions. In contrast, such cells of septic HFD mice utilize these routes only to spontaneously cast NETs, while after secondary ex vivo activation they exhibit so called "exhausted phenotype", which manifests itself in diminished NET release despite high glycolytic potential and flexibility to oxidize fatty acids. Moreover, impact of ATP synthase inhibition on NET formation is revealed. Overall, the study shows that the neutrophil potential to cast NETs depends on both the metabolic and inflammatory state of the individual.
dc.affiliationpl
Wydział Biologii : Instytut Zoologii i Badań Biomedycznych
dc.contributor.authorpl
Cichoń, Iwona - 178006
dc.contributor.authorpl
Ortmann, Weronika - 213274
dc.contributor.authorpl
Kołaczkowska, Elżbieta - 129011
dc.date.accessioned
2021-07-30T10:01:15Z
dc.date.available
2021-07-30T10:01:15Z
dc.date.issuedpl
2021
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
14
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
22
dc.identifier.articleidpl
7718
dc.identifier.doipl
10.3390/ijms22147718
dc.identifier.eissnpl
1422-0067
dc.identifier.issnpl
1661-6596
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/276625
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subject.enpl
immunometabolism
dc.subject.enpl
neutrophil extracellular traps
dc.subject.enpl
neutrophils
dc.subject.enpl
obesity
dc.subject.enpl
GLUT1
dc.subject.enpl
glycolysis
dc.subject.enpl
PPP pathway
dc.subject.enpl
fatty acids
dc.subject.enpl
ATP synthase
dc.subject.enpl
systemic inflammation
dc.subtypepl
Article
dc.titlepl
Metabolic pathways involved in formation of spontaneous and lipopolysaccharide-induced neutrophil extracellular traps (NETs) differ in obesity and systemic inflammation
dc.title.journalpl
International Journal of Molecular Sciences
dc.typepl
JournalArticle
dspace.entity.type
Publication

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