Surviving low oxygen

Hypoxia-inducible factor–1α (HIF-1α) prolongs the life of oxygen-deprived neutrophils by inducing NF-κB–driven survival signals, according to a study by Walmsley et al. on page 105. HIF-1α, a transcription factor induced by low oxygen, is required for myeloid cell function but has never been linked to myeloid apoptosis. Walmsley et al. now show that cells lacking this protein are robbed of the ability to resist apoptosis in low-oxygen environments like those encountered in wounds and inflamed tissues.

Neutrophils must function in adverse environments where oxygen and nutrient supplies are low. To do this, they turn on HIF-1α, which drives the synthesis of enzymes that make ATP anaerobically. In mice whose myeloid cells lack HIF-1α, the cells quickly lose their ATP supplies and thus have no energy to migrate or function in response to inflammatory stimuli.

Neutrophils also delay apoptosis during hypoxia, and the authors now show HIF-1α is required for this delay. The accelerated death could be mimicked in HIF-1α–positive cells by blocking NF-κB, suggesting a key role for this transcription factor in prolonging survival. The authors speculate that the ability of HIF-1α to induce neutrophil survival might contribute to a delayed resolution of inflammation, making a bad situation even worse.