Fatty Acid Binding Protein 5-deficiency impairs alveolar macrophage function and metabolism

Methods

Immune and metabolic responses were analyzed using functional assays, flow cytometry, ELISA, cell metabolic profiling and tracing, as well as ATAC-seq. Results: FABP5-/- mice exhibited impaired efferocytosis, reflected by a reduction of apoptotic cell engulfment by alveolar macrophages. This was accompanied by a reduction in fatty acid uptake and fatty acid -oxidation, a reduction in mitochondrial respiration, an accumulation of TCA cycle and glycolysis metabolites, and an increased chromatin accessibility for AP-1 family members.

Conclusions: FABP5-deficient alveolar macrophages failed to initiate reparative metabolic programming, which is critical for the resolution of inflammation. Our data suggest that increasing FABP5 expression could provide a metabolic switch that facilitates macrophage conversion to a pro-resolving phenotype and restores macrophage efferocytic functions in the lungs of COPD patients.