Decreased expression of hypoxia-inducible factor 1α (HIF-1α) in cord blood monocytes under anoxia

Background Infections are a major cause for morbidity and mortality in neonates; however, the underling mechanisms for increased infection susceptibility are incompletely understood. Hypoxia, which is present in inflamed tissues, has been identified as an important activation signal for innate immune cells in adults and is mainly mediated by hypoxia-inducible factor 1 alpha (HIF-1 alpha). Fetal tissue pO(2) physiologically is low but rises immediately after birth. Methods In this study, the effect of low oxygen partial pressure (pO(2)) on HIF-1 alpha expression and its targets phagocytosis, reactive oxygen species (ROS) production and vascular endothelial growth factor (VEGF) secretion was compared in vitro between immune cells from adult peripheral blood and cord blood using anoxia, HIF-1 alpha stabilizer desferroxamin (DFO) and E. coli as stimuli. Results We show that anoxia-induced HIF-1 alpha protein accumulation, phagocytosis, ROS-production and VEGF-expression were greatly diminished in cord blood compared to adult cells. E. coli led to HIF-1 alpha gene expression in adult and cord blood immune cells; however, cord blood cells failed to accumulate HIF-1 alpha protein and VEGF upon E. coli stimulation. Conclusions Taken together, our results show a diminished activation of cord blood immune cells by low pO(2), which might contribute to impaired reactivity in the context of infection. Impact Neonatal immune cells do not accumulate HIF-1 alpha under low oxygen partial pressure leading to decreased phagocytosis and decreased ROS production. We demonstrate a previously unknown mechanism of reduced activation of neonatal immune cells in the context of an inflammatory response. This could contribute to the increased susceptibility of newborns and preterm infants to infection.

Automated summary

This study compares the differences between adult and neonatal immune cells under low oxygen partial pressure. It finds that HIF-1 alpha expression, phagocytosis, ROS production, and VEGF secretion are significantly reduced in neonatal immune cells under hypoxic conditions. This may contribute to the decreased responsiveness of neonatal immune cells in the context of infection.