Blood Spotlight Macrophages and iron trafficking at the birth and death of red cells

It is important to beginwith the distinctive properties of iron and its role as an essential micronutrient. Iron itself or as a component of heme and iron-sulfur clusters is required for numerous biological processes. Additionally, iron’s reactivity makes it quite toxic because it is able to catalyze Fenton reactions and generate dangerous hydroxyl radicals. Similarly, imbalances in the biogenesis of iron-containing prosthetic groups, such as heme or iron-sulfur clusters, result in the buildup of toxic intermediates and subsequent pathologies, including anemia or porphyrias. Therefore, the trafficking and transport of iron and ironcontaining prosthetic groups must be carefully regulated at cellular and systemic levels. Iron is unique in how it is absorbed, stored, and mobilized in the body. Dietary iron is not readily absorbed because it is rendered insoluble at intestinal pH and by precipitating compounds found in food, and there are no specific iron excretion mechanisms in the body. Loss of iron can happen via blood loss and via desquamation of intestinal epithelial cells, where it is retained in ferritin when body iron stores are elevated. Women are more vulnerable to iron deficiencies because of monthly loss throughmenstrual bleeding, aswell as through pregnancy and childbirth. The greatest need for ironmobilization in the body is erythropoiesis. Asmuch as 70%of iron in the adult human body is found in the formof heme in hemoglobin in red blood cells (RBCs). Although;25 mg of iron is required per day for hemoglobin production and erythropoiesis, only 1 to 2mg per day is absorbed in the gut. Themajority of iron used for red cell formation therefore comes from iron recycled from senescent red blood cells. This review focuses on iron trafficking at both the birth and death of RBCs and the role thatmacrophages play in these physiological processes. We specifically focus on putative pathways for the transport of heme.