Abstract
The production of around 2.5 million red blood cells (RBCs) per second in erythropoiesis is one of the most intense activities in the body. It continuously consumes large amounts of iron, approximately 80% of which is recycled from aged erythrocytes. Therefore, similar to the “making”, the “breaking” of red blood cells is also very rapid and represents one of the key processes in mammalian physiology. Under steady-state conditions, this important task is accomplished by specialized macrophages, mostly liver Kupffer cells (KCs) and splenic red pulp macrophages (RPMs). It relies to a large extent on the engulfment of red blood cells via so-called erythrophagocytosis. Surprisingly, we still understand little about the mechanistic details of the removal and processing of red blood cells by these specialized macrophages. We have only started to uncover the signaling pathways that imprint their identity, control their functions and enable their plasticity. Recent findings also identify other myeloid cell types capable of red blood cell removal and establish reciprocal cross-talk between the intensity of erythrophagocytosis and other cellular activities. Here, we aimed to review the multiple and emerging facets of iron recycling to illustrate how this exciting field of study is currently expanding.
Highlights
Red blood cells (RBCs) or erythrocytes represent the most abundant cells in the human body, highly specialized for the shuffling of oxygen and carbon dioxide between the lungs and tissues
We will provide an update on the molecular mechanisms involved in the recognition and the removal of red blood cells, summarize insights into cues that mediate the development of iron-recycling cells and discuss reciprocal cross-talk between erythrophagocytosis intensity and other cellular functions of macrophages
For red pulp macrophages (RPMs), around 10% of cells are actively phagocytosing in a given moment, and, typically, one erythrocyte can be detected in one red pulp macrophage [44]
Summary
Red blood cells (RBCs) or erythrocytes represent the most abundant cells in the human body, highly specialized for the shuffling of oxygen and carbon dioxide between the lungs and tissues The binding of these gaseous particles is mediated by heme, an iron-containing prosthetic group that constitutes an integral part of the protein hemoglobin. The production of RBCs in a process called erythropoiesis is very rapid and yields approximately 200 billion RBCs daily, corresponding to 2.5 million every second [1] (Figure 1) This process tightly synchronizes intensive iron acquisition and the synthesis of heme with the translation of the globin polypeptides [2], which assemble stoichiometrically into hemoglobin composed of 2 α and 2 β globin chains, each biding one heme moiety. We will provide an update on the molecular mechanisms involved in the recognition and the removal of red blood cells, summarize insights into cues that mediate the development of iron-recycling cells and discuss reciprocal cross-talk between erythrophagocytosis intensity and other cellular functions of macrophages
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