2013
DOI: 10.4049/jimmunol.1201755
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Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

Abstract: Inflammatory conditions can profoundly alter human neutrophils, a leukocyte subset generally viewed as terminally differentiated and catabolic. In cystic fibrosis (CF) patients, neutrophils recruited to CF airways show active exocytosis and sustained phosphorylation of prosurvival, metabolic pathways. Because the CF airway lumen is also characterized by high levels of free glucose and amino acids, we compared surface expression of Glut1 (glucose) and ASCT2 (neutral amino acids) transporters, as well as that of… Show more

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Cited by 56 publications
(67 citation statements)
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“…However, the relevance of these murine findings to human conditions, particularly cystic fibrosis lung disease, remains to be established. Based on our previous experience [19] and this present study we have no evidence that CXCR4-expressing granulocytes in cystic fibrosis airways simply represent apoptotic or necrotic cells, but rather suggest that this granulocyte phenotype reflects microenvironmental adaption and cellular reprogramming, as proposed previously [20,21,35].…”
Section: Cxcr4supporting
confidence: 51%
“…However, the relevance of these murine findings to human conditions, particularly cystic fibrosis lung disease, remains to be established. Based on our previous experience [19] and this present study we have no evidence that CXCR4-expressing granulocytes in cystic fibrosis airways simply represent apoptotic or necrotic cells, but rather suggest that this granulocyte phenotype reflects microenvironmental adaption and cellular reprogramming, as proposed previously [20,21,35].…”
Section: Cxcr4supporting
confidence: 51%
“…Therefore, additional studies described that neutrophils migrating into CF airways can adapt to this enriched milieu by positively modulating their G-CSF receptor (CD114) (Makam et al, 2009) and their metabolite transporters, notably for glucose (GLUT1 or SLC2A1) and inorganic phosphate (PiT1 or SLC20A1) when compared to blood neutrophils. Interestingly, by looking directly into airway subsets, CF airway neutrophils displayed further regulation profile in PiT2 (or SLC20A2, another inorganic phosphate transporter) as well as in amino acid transporter (ASCT2 or SLC1A5), involved in the supplementation of essential amino acids regulating mTOR (Nicklin et al, 2009;Laval et al, 2013). Taken together, up-regulation of the anabolic prosurvival mTOR pathway and changes in surface receptors suggest that neutrophils homing to CF lungs undergo a concerted set of reprogramming processes.…”
Section: New Paradigm Of Airway Neutrophilsmentioning
confidence: 99%
“…Given the emerging concept of neutrophil heterogeneity and plasticity (Makam et al, 2009;Laval et al, 2013;Kruger et al, 2015), neutrophil phenotype-specific targeting approaches could be reasonable, but require further preclinical and clinical studies.…”
Section: Neutrophil-based Targeting Strategies and Their Implication mentioning
confidence: 99%
“…Denitrification during chronic lung infection in CF may also be used by other CF pathogens because we recently demonstrated the genetic setup for denitrification as well as anaerobic N 2 O production in Achromobacter xylosoxidans (43), an emerging CF pathogen that induces an inflammatory response resembling the response induced by P. aeruginosa (44). Consumption of glucose by activated PMNs (45,46) may lead to a reduction in available glucose, which may also limit the growth of P. aeruginosa (47,48). However, the high levels of glucose (2 to 4 mM) in CF airway fluids (49) suggest that bacterial growth in infected mucus is not limited by available glucose.…”
Section: Figmentioning
confidence: 99%