Blood and iron wars free#

Both of these responses are homeostatic under most conditions. Iron requirements of bone marrow erythropoiesis stimulate iron absorption in the small intestine, while excessive iron stores (accumulated predominantly in the liver) provide an inhibitory signal.

7ДЄnalysis of iron metabolism in human diseases and animal models suggests several major influences 2 that determine how much iron is absorbed from food and how much recycled iron is released from macrophages. For these or possibly other reasons, patients and mice with iron overload are more susceptible to a number of intracellular and blood pathogens, 5, 6 and even relatively modest increase in iron intake may diminish host resistance to infection. Conversely, bacteria grow faster and form biofilms more readily when iron is abundant. Iron deprivation may also inhibit the formation of resistant bacterial biofilms 4 and favor the mobile but vulnerable unicellular forms that are better equipped to reach alternative iron sources. Bacteria incur metabolic costs to obtain iron in iron-poor environments, and these may limit growth. The most highly adapted pathogens even evolved the ability to wrest iron from host iron-binding proteins such as hemoglobin, transferrin, and lactoferrin. These devices include the secretion of iron-binding organic molecules, siderophores, and their reuptake by bacteria (the avidly iron-binding desferroxamine is a siderophore).

Blood and iron wars free#

Bacteria have evolved multiple sophisticated mechanisms 3 for acquiring iron in environments where very little free iron is available. However, when dietary iron is more abundant, absorption is appropriately attenuated.ДЄnother reason why iron must be tightly controlled is that resistance to infection is in part dependent on the outcome of a tug-of-war over iron between the host and the invading bacteria. Such conservation of iron is essential because many human diets contain just enough iron to replace the small losses.

2 In comparison, the total body iron in an adult male is 3000 to 4000 mg and the daily iron requirement for erythropoiesis is about 20 mg. The loss of iron in a typical adult male is so small that it can be met by absorbing only 1 to 2 mg of iron per day. Humans and other vertebrates strictly conserve iron by recycling it from senescent erythrocytes and from other sources. 1 It is a key functional component of oxygen transporting and storage molecules (eg, hemoglobin and myoglobin) and of many enzymes that catalyze the redox reactions required for the generation of energy (eg, cytochromes), the production of various metabolic intermediates, and for host defense (eg, nicotinamide adenine dinucleotide phosphate oxidase). Iron is an essential element for nearly all living organisms. The discovery of hepcidin and its role in iron metabolism could lead to new therapies for hemochromatosis and anemia of inflammation. In anemia of inflammation, hepcidin production is increased up to 100-fold and this may account for the defining feature of this condition, sequestration of iron in macrophages. Recent evidence shows that deficient hepcidin response to iron loading may contribute to iron overload even in the much milder common form of hemochromatosis, from mutations in the HFE gene. The key role of hepcidin is confirmed by the presence of nonsense mutations in the hepcidin gene, homozygous in the affected members, in 2 families with severe juvenile hemochromatosis.

Evidence from transgenic mouse models indicates that hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from macrophages. The synthesis of hepcidin is greatly stimulated by inflammation or by iron overload. Human hepcidin, a 25вЂ“amino acid peptide made by hepatocytes, may be a new mediator of innate immunity and the long-sought iron-regulatory hormone.