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Background Alveolar macrophages (AMs) are known to influence the pathogenesis of idiopathic pulmonary fibrosis (IPF) and are said to express markers of hypoxic signalling in the fibrotic lung (PMID: 33805152). Hypoxia is suggested to directly affect fibroblasts and influence the fibrogenic cascade, however its impact on AM phenotype and function is unknown.Hypothesis Hypoxic conditions alter the immunometabolic phenotype of AMs, impacting their role in lung homeostasis.Method AMs were exposed to 1% oxygen for 48 hours and compared to normal culture conditions. AM function was measured by their ability to engulf apoptotic cells or ‘efferocytosis’. Specific antibody binding to AM cell surface markers was measured by flow cytometry. Single Cell ENergetic metabolism by profIling Translation inHibition (SCENITH) is a method used to examine global metabolic activity in a cell. This method harnesses puromycin to measure all protein synthesis in a cell as a surrogate measure of ATP production (PMID: 35497494). AMs were treated with oligomycin, an inhibitor of ATP synthase and the electron transport chain, or 2-deoxyglucose, a non-metabolisable glucose analogue, and changes in metabolic activity were measured.Results AMs exhibit a reduced capacity for efferocytosis in hypoxia (p=0.0156, n=7), alongside a reduction in scavenger receptor MerTK (p=0.0312, n=6). CD36 scavenger receptor surface expression is increased after exposure to hypoxia (0.0312, n=6). The global metabolic activity of AMs is reduced after exposure to hypoxia (p=0.0147, n=7). 2-deoxyglucose has no significant impact on metabolic activity of AMs in either condition. Oligomycin impairs metabolic activity in both normal cell culture conditions (p<0.0001, n=6) and in hypoxia (p=0.0281, n=6), indicating some reliance on oxidative phosphorylation regardless of oxygen supply.Abstract S90 Figure 1Conclusion AMs exhibit changes in function, phenotype and metabolism in hypoxia. The loss of ability to remove dead or damaged cells by efferocytosis would lead to prolonged disruption of the alveolar epithelium in the lung and may potentiate excessive wound healing and fibrosis. Decreased efferocytosis in hypoxia may be attributed to dysregulated efferocytosis receptor expression or decreased metabolic activity. Further research is needed to dissect the mechanism behind this dysfunction and to model how it could influence the pathogenesis of IPF.