Summary 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- 13 C 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.

The association between pulmonary hypertension (PH) and hypoxia is well-established, with two key mechanistic processes, hypoxic pulmonary vasoconstriction and hypoxia-induced vascular remodeling, driving changes in pulmonary arterial pressure. In contrast to other forms of pulmonary hypertension, the vascular changes induced by hypoxia are reversible, both in humans returning to sea-level from high altitude and in animal models. This raises the intriguing possibility that the molecular drivers of these hypoxic processes could be targeted to modify pulmonary vascular remodeling in other contexts. In this review, we outline the history of research into PH and hypoxia, before discussing recent advances in our understanding of this relationship at the molecular level, focussing on the role of the oxygen-sensing transcription factors, hypoxia inducible factors (HIFs). Emerging links between HIF and vascular remodeling highlight the potential utility in inhibiting this pathway in pulmonary hypertension and raise possible risks of activating this pathway using HIF-stabilizing medications.

In the originally published version of this article, an earlier draft of Figure 5 was mistakenly included. This has now been replaced with the final version, which includes data generated during the revision process. Updated figure panels now include bacterial killing of Staphylococcus aureus (SH1000) (Figure 5B), baseline ATP levels (Figure 5D), glycolytic response to SH1000 (Figures 5E and 5F), and tracing of U-13C glutamine into F1,6BP (Figure 5R). Figure 5G has been removed and replaced by 5E; 5L has been removed and replaced by 5D. The remaining panels have been renumbered in line with the figure legend and Results text. The figure legend in the originally published article is correct and corresponds to the updated figure. This error does not affect the data and conclusions of the paper. The authors sincerely apologize for any confusion that this error may have caused.