Abstract: 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.
Keywords: vitamin C; sepsis; neutrophils; NETosis; cell free DNA; nuclear factor κB
Export to BibTeX
MDPI and ACS Style
Mohammed, B.M.; Fisher, B.J.; Kraskauskas, D.; Farkas, D.; Brophy, D.F.; Fowler, A.A.; Natarajan, R. Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation. Nutrients 2013, 5, 3131-3150.
Mohammed BM, Fisher BJ, Kraskauskas D, Farkas D, Brophy DF, Fowler AA, Natarajan R. Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation. Nutrients. 2013; 5(8):3131-3150.
Mohammed, Bassem M.; Fisher, Bernard J.; Kraskauskas, Donatas; Farkas, Daniela; Brophy, Donald F.; Fowler, Alpha A.; Natarajan, Ramesh. 2013. "Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation." Nutrients 5, no. 8: 3131-3150.