By Gunter Weiss, Victor R. Gordeuk, Chaim Hershko
This booklet summarizes the most up-tp-date learn at the anemia of persistent sickness and identifies powerful diagnostic options for this universal medical condition-covering key themes relating to the layout and choice of healing ideas together with the therapy of the underlying sickness, the biology of erythropoietin and the law of erythropoiesis, the disturbance of iron homeostasis, and the advanced nature of the systemic inflammatory reaction.
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Extra info for Anemia of Chronic Disease (Basic and Clinical Oncology)
A recent analysis of gene expression profiles in duodenal samples from hfeÀ=À and hfeC282Y=C282Y mice showed increased expression of Dcytb mRNA, without any changes in the mRNA levels of DMT1 and ferroportin (50). It should be noted that duodenal crypt cells (83,84) and macrophages (85) from patients with HFE-related hemochromatosis are not only spared from iron overload, but also appear to be are iron-deficient. The viral delivery of wild-type HFE to cultured monocytes from such patients resulted in normalization of iron loading by Tf (86).
The development of severe anemia despite iron overload in hypotransferrinemias and atransferrinemias emphasizes the importance of Tf as the physiologically relevant donor of iron for erythropoiesis (39). Heme oxygenase (Hmox1) is involved in the catabolism of heme from senescent erythrocytes in macrophages and therefore plays a key role in iron reutilization by the erythron (4). As one would expect, Hmox1À=À mice suffer from microcytic anemia (73). In addition, these mice display severe pathological features, such as growth retardation, chronic inflammation, and tissue iron overload (paradoxically, nonheme iron) in the liver (hepatocytes and Kupffer cells) and in the kidney, despite low Tf saturation.
In the cytoplasm, iron is utilized for the synthesis of iron-containing proteins and excess is stored in ferritin. The pathway is completed by recycling of the apoTf–TfR complex to the cell surface and release of apoTf. Association of TfR1 with HFE impairs the binding of extracellular diferric-Tf and negatively regulates the cycle. Regulation of Iron Metabolism 19 synthesis of iron-containing proteins, or targeted to mitochondria for heme synthesis (a major event in erythroid cells). The transport of Fe(II) across the endosomal membrane is most likely mediated by DMT1 (57,109).