Normal and dysregulated crosstalk between iron metabolism and erythropoiesis

Abstract

Erythroblasts possess unique characteristics as they undergo differentiation from hematopoietic stem cells. During terminal erythropoiesis, these cells incorporate large amounts of iron in order to generate hemoglobin and ultimately undergo enucleation to become mature red blood cells, ultimately delivering oxygen in the circulation. Thus, erythropoiesis is a finely tuned, multifaceted process requiring numerous properly timed physiological events to maintain efficient production of 2 million red blood cells per second in steady state. Iron is required for normal functioning in all human cells, the erythropoietic compartment consuming the majority in light of the high iron requirements for hemoglobin synthesis. Recent evidence regarding the crosstalk between erythropoiesis and iron metabolism sheds light on the regulation of iron availability by erythroblasts and the consequences of insufficient as well as excess iron on erythroid lineage proliferation and differentiation. In addition, significant progress has been made in our understanding of dysregulated iron metabolism in various congenital and acquired malignant and non-malignant diseases. Finally, we report several actual as well as theoretical opportunities for translating the recently acquired robust mechanistic understanding of iron metabolism regulation to improve management of patients with disordered erythropoiesis, such as anemia of chronic inflammation, β-thalassemia, polycythemia vera, and myelodysplastic syndromes.

Cross-Modal Imaging Reveals Nanoparticle Uptake Dynamics in Hematopoietic Bone Marrow during Inflammation

“…While at first this may appear contradictoryconsidering that inflammation typically prompts a release of innate immune cells from the bone marrow , this phenomenon is in fact consistent with the established dynamics of iron recirculation to the erythroid marrow. The uptake of nanoparticles at the bone marrow under normal circumstances has been described in other studies employing iron oxide nanoparticle-enhanced imaging. ,, This enhanced bone marrow uptake during inflammation is actually in alignment with the recognized patterns of iron distribution, which include the recycling of iron back to the erythroid marrow where red blood cells are formeda process that is part of the body’s normal response to inflammation . Additionally, the reticuloendothelial system, a network of cells and tissues present in the spleen, liver, and bone marrow that is responsible for the sequestration of iron, plays a significant role in this context .…”

“…38 It captures and stores iron as part of the body's defense mechanism, holding it back from pathogens during an inflammatory response and influencing the distribution and retention of nanoparticles. 37 Our data suggest that the enhanced uptake of nanoparticles in the inflamed bone marrow resulted from increased permeability. This assertion is supported by our pre-CLIO contrast-enhanced MRI scans of the bone marrow.…”

“…Additionally, the reticuloendothelial system, a network of cells and tissues present in the spleen, liver, and bone marrow that is responsible for the sequestration of iron, plays a significant role in this context . It captures and stores iron as part of the body’s defense mechanism, holding it back from pathogens during an inflammatory response and influencing the distribution and retention of nanoparticles …”

“…32,44 Intravital microscopy demonstrated the real-time deceleration and accumulation of CLIO nanoparticles in the inflamed bone marrow, occurring as quickly as 10 min post intravenous injection in Cx3cr1 the gathering of iron-containing granules in proximity to sinusoidal endothelial cells. 45 The increased deceleration rate of particles during inflammation could be due to the bone marrow vascular niche's role in processing cellular waste, 37 such as aged red blood cells, atypical erythroblasts, and expelled nuclei. 45 This process plays a crucial role in recycling and delivering iron, ultimately ensuring the production of erythrocytes.…”

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria

“…35 Cell free hemoglobin is bound by haptoglobin (Hp) that is taken up by macrophages via CD163 for its recycling. 55 Oxidized hemoglobin has a reduced Hp biding and therefore a weaken interaction with human macrophages via CD163. 34 In the lung of mice infected with Spn, oxidized hemoglobin bound to a subset of Spn-Hb + bacteria that lacked capsule, suggesting that it protected Spn-Hb + from the cellular immune response.…”