Differential regulation of iron homeostasis during human macrophage polarized activation.
Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions, mimicked by the combined action of LPS and IFN-gamma (M1 polarization). However, macrophages can undergo an alternative type of activation stimulated by Th2 cytokines, and acquire a role in cell growth and tissue repair control (M2 polarization). We characterized the expression of genes related to iron homeostasis in fully differentiated unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1 macrophages showed changes in gene expression (ferroportin repression and H ferritin induction) that favour iron sequestration in the reticuloendothelial system, a hallmark of inflammatory disorders, whereas the M2 macrophages had an expression profile (ferroportin upregulation and the downregulation of H ferritin and heme oxygenase) that enhanced iron release. The conditioned media from M2 macrophages promoted cell proliferation more efficiently than those of M1 cells and the effect was blunted by iron chelation. The role of ferroportin-mediated iron release was demonstrated by the absence of differences from the media of macrophages of a patient with loss of function ferroportin mutation. The distinct regulation of iron homeostasis in M2 macrophages provides insights into their role under pathophysiological conditions.
Recalcati
Stefania
S
Department of Human Morphology and Biomedical Sciences "Città Studi", University of Milan, Milan, Italy.
Locati
Massimo
M
Marini
Agnese
A
Santambrogio
Paolo
P
Zaninotto
Federica
F
De Pizzol
Maria
M
Zammataro
Luca
L
Girelli
Domenico
D
Cairo
Gaetano
G
D000328:Adult; D015870:Gene Expression; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism*; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007501:Iron