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Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation

Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters NETosis...

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Autores principales: Mohammed, Bassem M., Fisher, Bernard J., Kraskauskas, Donatas, Farkas, Daniela, Brophy, Donald F., Fowler, Alpha A., Natarajan, Ramesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775246/
https://www.ncbi.nlm.nih.gov/pubmed/23939536
http://dx.doi.org/10.3390/nu5083131
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author Mohammed, Bassem M.
Fisher, Bernard J.
Kraskauskas, Donatas
Farkas, Daniela
Brophy, Donald F.
Fowler, Alpha A.
Natarajan, Ramesh
author_facet Mohammed, Bassem M.
Fisher, Bernard J.
Kraskauskas, Donatas
Farkas, Daniela
Brophy, Donald F.
Fowler, Alpha A.
Natarajan, Ramesh
author_sort Mohammed, Bassem M.
collection PubMed
description Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo(−/−) mice as they lack the ability to synthesize VitC. Sepsis was induced by intraperitoneal infusion of a fecal stem solution (abdominal peritonitis, FIP). Some VitC deficient Gulo(−/−) mice received an infusion of ascorbic acid (AscA, 200 mg/kg) 30 min after induction of FIP. NETosis was assessed histologically and by quantification for circulating free DNA (cf-DNA) in serum. Autophagy, histone citrullination, endoplasmic reticulum (ER) stress, NFκB activation and apoptosis were investigated in peritoneal PMNs. Results: Sepsis produced significant NETs in the lungs of VitC deficient Gulo(−/−) mice and increased circulating cf-DNA. This was attenuated in the VitC sufficient Gulo(−/−) mice and in VitC deficient Gulo(−/−) mice infused with AscA. Polymorphonuclear neutrophils (PMNs) from VitC deficient Gulo(−/−) mice demonstrated increased activation of ER stress, autophagy, histone citrullination, and NFκB activation, while apoptosis was inhibited. VitC also significantly attenuated PMA induced NETosis in PMNs from healthy human volunteers. Conclusions: Our in vitro and in vivo findings identify VitC as a novel regulator of NET formation in sepsis. This study complements the notion that VitC is protective in sepsis settings.
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spelling pubmed-37752462013-09-17 Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation Mohammed, Bassem M. Fisher, Bernard J. Kraskauskas, Donatas Farkas, Daniela Brophy, Donald F. Fowler, Alpha A. Natarajan, Ramesh Nutrients Article Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo(−/−) mice as they lack the ability to synthesize VitC. Sepsis was induced by intraperitoneal infusion of a fecal stem solution (abdominal peritonitis, FIP). Some VitC deficient Gulo(−/−) mice received an infusion of ascorbic acid (AscA, 200 mg/kg) 30 min after induction of FIP. NETosis was assessed histologically and by quantification for circulating free DNA (cf-DNA) in serum. Autophagy, histone citrullination, endoplasmic reticulum (ER) stress, NFκB activation and apoptosis were investigated in peritoneal PMNs. Results: Sepsis produced significant NETs in the lungs of VitC deficient Gulo(−/−) mice and increased circulating cf-DNA. This was attenuated in the VitC sufficient Gulo(−/−) mice and in VitC deficient Gulo(−/−) mice infused with AscA. Polymorphonuclear neutrophils (PMNs) from VitC deficient Gulo(−/−) mice demonstrated increased activation of ER stress, autophagy, histone citrullination, and NFκB activation, while apoptosis was inhibited. VitC also significantly attenuated PMA induced NETosis in PMNs from healthy human volunteers. Conclusions: Our in vitro and in vivo findings identify VitC as a novel regulator of NET formation in sepsis. This study complements the notion that VitC is protective in sepsis settings. MDPI 2013-08-09 /pmc/articles/PMC3775246/ /pubmed/23939536 http://dx.doi.org/10.3390/nu5083131 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Mohammed, Bassem M.
Fisher, Bernard J.
Kraskauskas, Donatas
Farkas, Daniela
Brophy, Donald F.
Fowler, Alpha A.
Natarajan, Ramesh
Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title_full Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title_fullStr Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title_full_unstemmed Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title_short Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
title_sort vitamin c: a novel regulator of neutrophil extracellular trap formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775246/
https://www.ncbi.nlm.nih.gov/pubmed/23939536
http://dx.doi.org/10.3390/nu5083131
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