Liver X receptor activation stimulates iron export in human alternative macrophages. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Circulation Research Year : 2013

Liver X receptor activation stimulates iron export in human alternative macrophages.


RATIONALE: In atherosclerotic plaques, iron preferentially accumulates in macrophages where it can exert pro-oxidant activities. OBJECTIVE: The objective of this study was, first, to better characterize the iron distribution and metabolism in macrophage subpopulations in human atherosclerotic plaques and, second, to determine whether iron homeostasis is under the control of nuclear receptors, such as the liver X receptors (LXRs). METHODS AND RESULTS: Here we report that iron depots accumulate in human atherosclerotic plaque areas enriched in CD68 and mannose receptor (MR)-positive (CD68(+)MR(+)) alternative M2 macrophages. In vitro IL-4 polarization of human monocytes into M2 macrophages also resulted in a gene expression profile and phenotype favoring iron accumulation. However, M2 macrophages on iron exposure acquire a phenotype favoring iron release, through a strong increase in ferroportin expression, illustrated by a more avid oxidation of extracellular low-density lipoprotein by iron-loaded M2 macrophages. In line, in human atherosclerotic plaques, CD68(+)MR(+) macrophages accumulate oxidized lipids, which activate LXRα and LXRβ, resulting in the induction of ABCA1, ABCG1, and apolipoprotein E expression. Moreover, in iron-loaded M2 macrophages, LXR activation induces nuclear factor erythroid 2-like 2 expression, thereby increasing ferroportin expression, which, together with a decrease of hepcidin mRNA levels, promotes iron export. CONCLUSIONS: These data identify a role for M2 macrophages in iron handling, a process regulated by LXR activation.
Fichier principal
Vignette du fichier
Bories_et_al_R2.pdf (716.17 Ko) Télécharger le fichier
inserm-00870992_edited.pdf (376.42 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00870992 , version 1 (14-03-2014)



Gael Bories, Sophie Colin, Jonathan Vanhoutte, Bruno Derudas, Corinne Copin, et al.. Liver X receptor activation stimulates iron export in human alternative macrophages.. Circulation Research, 2013, 113 (11), pp.1196-205. ⟨10.1161/CIRCRESAHA.113.301656⟩. ⟨inserm-00870992⟩
237 View
544 Download



Gmail Facebook X LinkedIn More