TABLE 3.
Metabolism of neutrophils during ROS production.
| References | Cells | Treatment/condition | Effect on metabolism | Associated effect | ROS | Readouts | PMID |
|---|---|---|---|---|---|---|---|
| Baillet et al. (2017) | Human healthy neutrophils and PLB985 cells | PMA, fMLP | ↑ Glycolysis | ↑ pPFK-2 | ↑ | Stimulation leads to an increase of the glycolysis rate and PFK-2 inhibition prevents both hyperglycolysis, leading to a decrease in ATP concentration and NADPH oxidase activation | 27799347 |
| PFK-2 inhibitor | ↓ Glycolysis | ↓ NADPH oxidase | ↓* | ||||
| Petty et al. (2005) | Human healthy neutrophils (pregnant or not) | Glucose | ↑ PPP | ↑ (and ↑ NO) | Neutrophils mainly use the PPP for ROS generation in high-glucose conditions. The inhibition of PPP and NOX attenuates high glucose-induced ROS generation in neutrophils | 16390806 | |
| PPP and NAD(P)H oxidase (NOX) inhibitor | ↓ PPP (by PPP inhibitor) | ↓* | |||||
| Britt et al. (2022) | Human healthy neutrophils and HL-60 cells | Zymozan, TNFα, fMLP and PMA | ↑ PPP and glycolysis mediators | ↑ NOX-dependent OCR | ↑ | Neutrophil stimulation causes rapid (10 or 30 min) metabolic changes. Activated neutrophils shift to PPP to increase NADPH production for oxidative burst and other effector functions | 35347316 |
| PPP and NOX inhibitors | ↓ PPP (by PPP inhibitor) no effect on glycolysis | ↓ NOX-dependent OCR | ↓* | ||||
| Furukawa et al. (2000) | Neutrophils from patients undergoing major gastrointestinal surgery | Basal | ↓ Glutaminolysis | ↓ Phagocytosis | ↓ | Glutamine supplementation enhances phagocytosis and production of reactive oxygen intermediates in patients that underwent major gastrointestinal surgery | 10793298 |
| Glutamine | ↑ Glutaminolysis | ↑ Phagocytosis | ↑ | ||||
| Rice et al. (2018) | Mouse bone marrow-derived neutrophils | PMA | ↑ OCR | ↑ (↑ H2O2) | ROS production requires two distinct metabolic pathways, with glucose metabolism required for early phase ROS and mitochondrial function only facilitating the late phase. Neutrophils adapt to glucose-limited environments by using mitochondrial FAO for ROS production via NADPH oxidase | 30504842 | |
| Glycolysis inhibitor | ↓ early-phase OCR | ↓ (↓ H2O2)* | |||||
| Mitochondrial respiration inhibition | ↓ late-phase OCR | ↓ (↓ H2O2) in late phase* | |||||
| FAO inhibition or mitochondrial respiration inhibition in conditions of glucose usage blockade | ↓ OCR | ↓ (↓ H2O2)* | |||||
| Tambralli et al. (2024) | Human healthy neutrophils | PMA | ↑ | Inhibiting either glycolysis or the PPP tempered PMA and APS IgG-induced ROS production | 38869951 | ||
| Ca ionophore A23187 (Ca iono) | No effect | ||||||
| Antiphospholipid syndrome (APS) IgG (vs. control IgG) | ↑ Glycolysis and PPP | Slow and persistent ↑ in ECAR/OCR; ↑ Lactate, G6P (after 1 h), NAPDH (after 1 and 2 h) and intracellular glycogen |
↑ | ||||
| 2-DG (glycolysis inhibitor) | ↓ Glycolysis ↓ PPP |
↓ Lactate | ↓ H2O2 (for PMA and APS IgG induced) | ||||
| G6PDi-1 (G6PD inhibitor) | ↓ PPP | ↓ G6PD activity | |||||
| DPI (NOX inhibitor) | |||||||
| GPI (Glycogenolysis inhibitor); in glucose-free media |
* = vs. stimulated cells without inhibition of the metabolic pathway. FAO, fatty acid oxidation; fMLP, N-Formyl-methionyl-leucyl-phenylalanine; G6PD, glucose-6-phosphate dehydrogenase; OCR, oxygen consumption rate; PFK-2, phosphofructokinase-2; PMA, phorbol myristate acetate; PPP, pentose phosphate pathway; ROS, reactive oxygen species; NOX, NADPH oxidase; TNF, tumor necrosis factor.