Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.

ABSTRACT: Resident-tissue macrophages (RTMs) arise from embryonic precursors^1,2, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15^-/- mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E₂ production. A compromised AM compartment resulted in increased susceptibility to acute lung injury induced by lipopolysaccharide and to pulmonary infections

SUBMITTER: Pernet E 

PROVIDER: S-EPMC9945843 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature