Impact of Short-Term Systemic Hypoxia on Phagocytosis, Cytokine Production, and Transcription Factor Activation in Peripheral Blood Cells

Abstract

Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+ T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .

Hypoxic regulation of neutrophil function and consequences for Staphylococcus aureus infection

“…Neutrophils obtained from acutely hypoxic volunteers (whole blood or purified cells) showed enhanced phagocytosis of zymosan [62] and E. coli, with enhanced expression of opsonic (FCgIIIbR) and complement (C1qRp and C5aR) receptors [56], which are important for pathogen recognition and ingestion. Interaction with matrix proteins further increased FCgR expression in the setting of hypoxia [63], which may reflect the in vivo environment more accurately.…”

Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis

“…Neutrophils obtained from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display increased survival times and enhanced phagocytic capacity 12 . In vitro studies have demonstrated that stabilization of HIF with DMOG prolonged neutrophil survival 13 and HIF stabilization by hypoxic incubation enhanced bacterial phagocytosis by neutrophils 14 and macrophages 15 . Further, DMOG treatment ameliorated disease in a murine model of endotoxic shock, through suppression of inflammatory cytokines and enhanced IL-10 production 16 .…”

Effect of moderate exercise under hypoxia on Th1/Th2 cytokine balance

“…There was no change in plasma TNF-α after the exercise under the hypoxia condition, suggesting that the action of IL-6 inhibits the expression of TNF-α in skeletal muscle. 30 It has been reported that hypoxia is a potent inflammatory agent, activating the NF-KB pathway and resulting in the release of TNF-α, orchestrating immune responses, tissue homeostasis 31,32 and inflammation in human beings and rodents. 33 However, the exercise performed at moderate hypoxia was able to inhibit the production of TNF-α, confirming previous studies.…”