Reactive oxygen species and iron--a dangerous partnership in inflammation

Cells of nearly all forms of life require well-defined amounts of iron for survival, replication and expression of differentiated processes. It has a central role in erythropoiesis but is also involved in many other intracellular processes in the tissues of the body. It is the fourth most abundant element in the Earth's crust and the most abundant transition metal in living organisms for which its characteristic chemistry endows it with a series of properties enabling it to fulfil certain biological reactions especially those involving redox mechanisms. It is involved in the transport of oxygen, in electron transfer, in the synthesis of DNA, in oxidations by oxygen (O2) and hydrogen peroxide (H2O2) and in many other processes maintaining normal structure and function of virtually all mammalian cells. Because an iron atom can exist in two valency states, ferrous and ferric, iron became the primordial partner of oxygen in evolution. However, as de Sousa et al. (1989) state, such long standing partnerships have to use protective devices to ensure that the toxicity of neither partner is expressed in the presence of the other. Here, we discuss this dangerous partnership and its relevance to inflammation. The main themes of this review are the known roles of iron in the generation of reactive oxygen intermediates and new developments, including iron and transcription and the reaction of iron with nitric oxide. We also consider the widening recognition of the importance of oxygen metabolites in hypoxia-reperfusion injury and disease of the skin and joint.