1. Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.
- Author
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Pernet E, Sun S, Sarden N, Gona S, Nguyen A, Khan N, Mawhinney M, Tran KA, Chronopoulos J, Amberkar D, Sadeghi M, Grant A, Wali S, Prevel R, Ding J, Martin JG, Thanabalasuriar A, Yipp BG, Barreiro LB, and Divangahi M
- Subjects
- Animals, Mice, Acute Lung Injury, Animals, Newborn, Arachidonate 12-Lipoxygenase deficiency, Arachidonate 15-Lipoxygenase deficiency, COVID-19, Influenza A virus, Lipopolysaccharides, Lung cytology, Lung virology, Orthomyxoviridae Infections, Prostaglandins E, SARS-CoV-2, Disease Susceptibility, 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid metabolism, Cell Self Renewal, Macrophages, Alveolar cytology, Macrophages, Alveolar metabolism, Neutrophils metabolism
- 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 with influenza A virus or SARS-CoV-2. Our results highlight the complexity of prenatal RTM programming and reveal their dependency on in trans eicosanoid production by neutrophils for lifelong self-renewal., (© 2023. The Author(s).)- Published
- 2023
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