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Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis
Cell Metabolism ( IF 27.7 ) Pub Date : 2020-12-10 , DOI: 10.1016/j.cmet.2020.11.016
Pranvera Sadiku 1 , Joseph A Willson 2 , Eilise M Ryan 2 , David Sammut 3 , Patricia Coelho 2 , Emily R Watts 2 , Robert Grecian 2 , Jason M Young 2 , Martin Bewley 3 , Simone Arienti 2 , Ananda S Mirchandani 2 , Manuel A Sanchez Garcia 2 , Tyler Morrison 2 , Ailing Zhang 2 , Leila Reyes 2 , Tobias Griessler 2 , Privjyot Jheeta 2 , Gordon G Paterson 2 , Christopher J Graham 2 , John P Thomson 4 , Kenneth Baillie 5 , A A Roger Thompson 3 , Jessie-May Morgan 2 , Abel Acosta-Sanchez 6 , Veronica M Dardé 6 , Jordi Duran 7 , Joan J Guinovart 8 , Gio Rodriguez-Blanco 9 , Alex Von Kriegsheim 9 , Richard R Meehan 4 , Massimiliano Mazzone 10 , David H Dockrell 2 , Bart Ghesquiere 6 , Peter Carmeliet 11 , Moira K B Whyte 2 , Sarah R Walmsley 2
Affiliation  

Neutrophils can function and survive in injured and infected tissues, where oxygen and metabolic substrates are limited. Using radioactive flux assays and LC-MS tracing with U-13C glucose, glutamine, and pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis and glycogenesis for effective survival and bacterial killing. These metabolic adaptations are dynamic, with net increases in glycogen stores observed following LPS challenge or altitude-induced hypoxia. Neutrophils from patients with chronic obstructive pulmonary disease have reduced glycogen cycling, resulting in impaired function. Metabolic specialization of neutrophils may therefore underpin disease pathology and allow selective therapeutic targeting.



中文翻译:

中性粒细胞通过糖异生和糖原生成促进有效的免疫反应

中性粒细胞可以在氧气和代谢底物有限的受伤和感染组织中发挥作用并存活。使用放射性通量测定和 LC-MS 追踪 U- 13 C 葡萄糖、谷氨酰胺和丙酮酸,我们观察到中性粒细胞需要通过糖异生和糖原生成来产生细胞内糖原储存,以有效存活和杀死细菌。这些代谢适应是动态的,在 LPS 挑战或海拔诱导的缺氧后观察到糖原储存的净增加。慢性阻塞性肺病患者的中性粒细胞减少了糖原循环,导致功能受损。因此,中性粒细胞的代谢特化可能支持疾病病理学并允许选择性治疗靶向。

更新日期:2021-02-02
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