Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.

ABSTRACT: Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such as macrophages, that inhabit harsh physiological environments. Here, we find that macrophages display enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterized by increased internalization and accelerated degradation of ACs. Transcriptional and translational analyses revealed that chronic physiological hypoxia induces two distinct but complimentary states. The first, "primed" state, consists of concomitant transcription and translation of metabolic programs in AC-naive macrophages that persist during efferocytosis. The second, "poised" state, consists of transcription, but not translation, of phagocyte function programs in AC-naive macrophages that are translated during efferocytosis.

SUBMITTER: Wang YT 

PROVIDER: S-EPMC9908853 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature