Iron is a vital element required for several biologic functions, first of all oxygen delivery to tissues, which occurs through the iron-containing molecule heme within red blood cells (RBC). Iron also plays key roles in inflammation and infections: on the one hand, iron is needed for a proper function of the immune system but, on the other, too much iron promotes the growth of microorganisms.
Macrophages are crucial cells of the innate immune system that have two important functions: 1) to remove old RBCs from blood and store heme-derived iron; 2) to ”eat” and kill pathogens, including bacteria, virus and fungi. Therefore macrophages are essential both for iron metabolism and protection from infections.
Several pathologic conditions are associated with excessive iron accumulation in macrophages, including transfusion-dependent anemia, where transfused RBCs are removed by macrophages; sickle cell disease, and anemia treated with intravenous iron preparations, where free heme and iron are accumulated in macrophages, respectively.
The focus of our research was to study whether iron accumulation in these three different pathologic conditions causes macrophage inflammation and the production of inflammatory molecules and analyze the consequences. Our results show that transfusions suppress inflammation. This effect may predispose transfused patients to severe infections, eventually leading to organ failure. On the contrary, free heme and iron have an inflammatory action on macrophages, which is worsened during infections. This effect causes chronic inflammation and tissue damage in sickle patients and patients treated with iron.
We conclude that different forms of iron accumulation in macrophages (RBCs versus free heme and iron) in different diseases, show opposite effects on inflammation. Our data suggest that molecules able to bind iron have therapeutic benefit on these diseases, through the modulation of these processes.
Presenter: Dr Francesca Vinchi
Affiliation: Iron Research Laboratory, New York Blood Center, New York, USA
Topic: CHRONIC RED BLOOD CELL TRANSFUSIONS IMPAIR THE INNATE IMMUNE RESPONSE TO INFECTIOUS CUES BY SHAPING MACROPHAGES TOWARDS AN ANTI-INFLAMMATORY FUNCTIONAL PHENOTYPE
Abstract S152 will be presented by Francesca Vinchi on Friday, June 15, 16:30-16:45 in Room A1.
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STOCKHOLM, June 15, 2018 /PRNewswire/ —