Polarization dictates iron handling by inflammatory and alternatively activated macrophages
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Polarization dictates iron handling by inflammatory and alternatively activated macrophages. / Corna, G.; Campana, L.; Pignatti, E.; Castiglioni, A.; Tagliafico, E.; Bosurgi, L.; Campanella, A.; Brunelli, S.; Manfredi, A.A.; Apostoli, P.; Silvestri, L.; Camaschella, C.; Rovere-Querini, P.
In: HAEMATOLOGICA, Vol. 95, No. 11, 2010, p. 1814-1822.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Polarization dictates iron handling by inflammatory and alternatively activated macrophages
AU - Corna, G.
AU - Campana, L.
AU - Pignatti, E.
AU - Castiglioni, A.
AU - Tagliafico, E.
AU - Bosurgi, L.
AU - Campanella, A.
AU - Brunelli, S.
AU - Manfredi, A.A.
AU - Apostoli, P.
AU - Silvestri, L.
AU - Camaschella, C.
AU - Rovere-Querini, P.
PY - 2010
Y1 - 2010
N2 - BackgroundMacrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.Design and MethodsInflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells.ResultsM1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective.ConclusionsCytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).
AB - BackgroundMacrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.Design and MethodsInflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells.ResultsM1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective.ConclusionsCytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-78149250305&partnerID=MN8TOARS
U2 - 10.3324/haematol.2010.023879
DO - 10.3324/haematol.2010.023879
M3 - SCORING: Journal article
C2 - 20511666
VL - 95
SP - 1814
EP - 1822
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 11
ER -
