Differential regulation of iron homeostasis during human macrophage polarized activation
Differential regulation of iron homeostasis during human macrophage polarized activation
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DOI：
10.1002/eji.200939889
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Cairo, Gaetano
中科院分区：
文献类型：
--
作者：
Recalcati, Stefania;Locati, Massimo;Cairo, Gaetano
炎症中的铁代谢主要在暴露于病原体或炎症条件的巨噬细胞中表征，通过LPS和IFN-γ的联合作用（M1极化）模拟。然而，巨噬细胞可以经历由Th 2细胞因子刺激的替代类型的活化，并且在细胞生长和组织修复控制（M2极化）中获得作用。我们的特点表达的基因与铁稳态在完全分化的非极化（M0），M1和M2人类巨噬细胞。M1巨噬细胞的分子特征显示了基因表达的变化（膜铁转运蛋白抑制和H铁蛋白诱导），有利于网状内皮系统中的铁螯合，这是炎症性疾病的标志，而M2巨噬细胞具有增强铁释放的表达谱（膜铁转运蛋白上调和H铁蛋白和血红素加氧酶下调）。M2巨噬细胞的条件培养基比M1细胞更有效地促进细胞增殖，并且该作用被铁螯合物钝化。膜铁转运蛋白介导的铁释放的作用通过与膜铁转运蛋白功能丧失突变患者的巨噬细胞培养基不存在差异来证明。M2巨噬细胞中铁稳态的独特调节提供了对它们在病理生理条件下作用的见解。
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.