Hemoglobin is the major oxygen-carrying system of the blood, but has many potentially dangerous side effects due to the redox reactions of the heme-bound iron and oxygen. Extracellular hemoglobin, resulting from hemolysis or exogenous infusion, exerts toxic effects that are major components in the pathogenesis of many diseases and iatrogenic situations, including hemolytic anemias and transfusion-induced intravascular hemolysis, preeclampsia, intraventricular hemorrhage, sickle cell disease and chronic inflammatory leg ulcers, and infusion of recombinant hemoglobin. The pathogenesis involves one-electron reactions between oxy-Hb, its downstream metabolites heme, iron, ROS and free radicals (NO, superoxide etc.) and exposed tissue components. Besides, release of extracellular hemoglobin can result in the removal of beneficial free radical species (e.g. nitric oxide) and/or the production of reactive free radicals on the globin protein itself. By the assembly of world-leading interdisciplinary experts this "Research Topic" proposal intends to outline the latest discoveries regarding the pathophysiology of extracellular hemoglobin – from molecular mechanisms to clinical significance. Furthermore, it will describe naturally occurring protection mechanisms that have evolved over time (i.e. haptoglobin, hemopexin, heme oxygenase and alpha-1-microglobulin). Finally, future therapeutic opportunities will be presented.
Hemoglobin is the major oxygen-carrying system of the blood, but has many potentially dangerous side effects due to the redox reactions of the heme-bound iron and oxygen. Extracellular hemoglobin, resulting from hemolysis or exogenous infusion, exerts toxic effects that are major components in the pathogenesis of many diseases and iatrogenic situations, including hemolytic anemias and transfusion-induced intravascular hemolysis, preeclampsia, intraventricular hemorrhage, sickle cell disease and chronic inflammatory leg ulcers, and infusion of recombinant hemoglobin. The pathogenesis involves one-electron reactions between oxy-Hb, its downstream metabolites heme, iron, ROS and free radicals (NO, superoxide etc.) and exposed tissue components. Besides, release of extracellular hemoglobin can result in the removal of beneficial free radical species (e.g. nitric oxide) and/or the production of reactive free radicals on the globin protein itself. By the assembly of world-leading interdisciplinary experts this "Research Topic" proposal intends to outline the latest discoveries regarding the pathophysiology of extracellular hemoglobin – from molecular mechanisms to clinical significance. Furthermore, it will describe naturally occurring protection mechanisms that have evolved over time (i.e. haptoglobin, hemopexin, heme oxygenase and alpha-1-microglobulin). Finally, future therapeutic opportunities will be presented.