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Chapter 46 : Macrophages and Iron Metabolism
Macrophages perform a vast range of biological functions, including regulation of embryonic development; scavenging and recycling of redundant, aged, or injured cells; modulation of tissue repair; and coordination and effector activity in host defense. By recycling and storing iron from senescent erythrocytes and other damaged cells, the macrophage controls iron homeostasis, supplying most of the iron needed for hemoglobin synthesis in erythrocyte precursors, and for the much smaller but important iron requirements of other cell populations. The macrophages serve a crucial regulatory role by functioning as a regulated storage compartment for iron. In response to systemic iron requirements, the release of iron from macrophages into plasma is negatively regulated by the interaction of the hepatic hormone hepcidin with its receptor/iron exporter ferroportin. In humans, macrophages contribute most of the iron entering the plasma compartment, with the rest of the iron influx into plasma made up from duodenal iron absorption and release of stored iron from hepatocytes. During infection and inflammation, interleukin-6, and to a lesser extent other cytokines, increases hepcidin synthesis. Hepcidin binds to macrophage ferroportin, induces its endocytosis and proteolysis, and thereby causes iron sequestration in macrophages. The resulting decrease in iron availability in other tissues can limit the growth and pathogenicity of invading extracellular microbes and is as an important means of host defense. Finally, bone marrow macrophages also have an important role in supporting efficient and rapid production of erythrocytes. The involvement of macrophages in iron metabolism thus serves both trophic and host defense functions. This review addresses the role of macrophages in iron metabolism in all these contexts, and represents an update and expansion of my previous discussion of the same subject ( 1 ).