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oai:repisalud.isciii.es:20.500.12105/65392024-09-27T10:01:22Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Izquierdo-Fernandez, Helena Maria author Brandi, Paola author Gomez, Manuel J author Conde-Garrosa, Ruth author Priego, Elena author Enamorado, Michel author Martinez-Cano, Sarai author Sanchez, Iris author Conejero, Laura author Jimenez-Carretero, Daniel author Martin-Puig, Silvia author Guilliams, Martin author Sancho, David author 2018 The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11c Delta Vhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo. VHL-deficient phenotype is intrinsic in AMs derived from monocyte precursors in mixed bone marrow chimeras. Moreover, unlike control Vhl(fl/fl), AMs from CD11c Delta Vhl mice do not reverse pulmonary alveolar proteinosis when transplanted into Csf2rb(-/)(-) mice, demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our results suggest that optimal AM terminal differentiation, self-renewal, and homeostatic function requires their intact oxygen-sensing capacity. Cell Rep. 2018; 24(7):1738-1746 10.1016/j.celrep.2018.07.034 2211-1247 Cell Reports 30110631 http://hdl.handle.net/20.500.12105/6539 TISSUE-RESIDENT MACROPHAGES COLONY-STIMULATING FACTOR GM-CSF FETAL MONOCYTES HYPOXIA DEVELOP LUNG MICE INFLAMMATION HIF-1-ALPHA Von Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal Differentiation, Self-Renewal, and Function