2026-07-21T20:40:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65392024-09-27T10:01:22Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fondation ACTERIA (Acting on European Research in Immunology and Allergology)
funder
Atresmedia
funder
Fundación La Marató TV3
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2018-10-26T07:59:27Z
2018-10-26T07:59:27Z
2018
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
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.
eng
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
journal article
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VonHippel-LindauProtein_2018.pdf
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VonHippel-LindauProtein_2018_SupplMat.pdf
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VonHippel-LindauProtein_2018.pdf.txt
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VonHippel-LindauProtein_2018_SupplMat.pdf.txt