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Regulation of tissue iron homeostasis: the macrophage “ferrostat”
Nathan C. Winn, … , Katrina M. Volk, Alyssa H. Hasty
Nathan C. Winn, … , Katrina M. Volk, Alyssa H. Hasty
Published January 30, 2020
Citation Information: JCI Insight. 2020;5(2):e132964. https://doi.org/10.1172/jci.insight.132964.
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Regulation of tissue iron homeostasis: the macrophage “ferrostat”

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Abstract

Iron is an essential element for multiple fundamental biological processes required for life; yet iron overload can be cytotoxic. Consequently, iron concentrations at the cellular and tissue level must be exquisitely governed by mechanisms that complement and fine-tune systemic control. It is well appreciated that macrophages are vital for systemic iron homeostasis, supplying or sequestering iron as needed for erythropoiesis or bacteriostasis, respectively. Indeed, recycling of iron through erythrophagocytosis by splenic macrophages is a major contributor to systemic iron homeostasis. However, accumulating evidence suggests that tissue-resident macrophages regulate local iron availability and modulate the tissue microenvironment, contributing to cellular and tissue function. Here, we summarize the significance of tissue-specific regulation of iron availability and highlight how resident macrophages are critical for this process. This tissue-dependent regulation has broad implications for understanding both resident macrophage function and tissue iron homeostasis in health and disease.

Authors

Nathan C. Winn, Katrina M. Volk, Alyssa H. Hasty

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Figure 1

Overview of Mɸ iron metabolism.

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Overview of Mɸ iron metabolism.
The uptake of Tf-bound Fe3+ is mediated ...
The uptake of Tf-bound Fe3+ is mediated by TfR1. CD163 and LRP1 (also known as CD91) mediate the uptake of Hb-Hp and Hx-heme, respectively. Intracellular heme-Fe (extracted from Hb-Hp and Hx-heme) is catabolized by HO-1 for incorporation into the cellular ferritin pool or trafficked into the mitochondria. Non-Tf-bound iron (NTBI) is imported via DMT1. Iron export by Fpn is facilitated by Cp, which oxidizes Fe2+ to Fe3+ to allow sequestration by apo-Tf. Tf, transferrin; TfR1, transferrin receptor 1; LRP/CD91, LDL-related receptor 1/CD91; DMT1, divalent metal transporter 1; Hb-Hp, hemoglobin-haptoglobin; Hx-heme, hemopexin-heme; HO-1, heme oxygenase 1; Ft-H, ferritin heavy chain 1; Ft-L, ferritin light chain; Fpn, ferroportin; Cp, ceruloplasmin.

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