Haptoglobin, hemopexin, and related defense pathways—basic science, clinical perspectives, and drug development

摘要: Hemolysis, which occurs in many disease states, can trigger a diverse pathophysiologic cascade that is related to the specific biochemical activities of free Hb and its porphyrin component heme. Normal erythropoiesis concomitant removal senescent red blood cells (RBC) from circulation at rates approximately 2x106 RBCs/second. Within this physiologic range RBC turnover, small fraction hemoglobin (Hb) released into plasma as extracellular Hb. In humans, there an efficient multicomponent system sequestration, oxidative neutralization clearance. Haptoglobin (Hp) primary Hb-binding protein human plasma, attenuates adverse effects The cellular receptor target Hp monocyte/macrophage scavenger receptor, CD163. Following Hb-Hp binding CD163, internalization complex leads globin heme metabolism, followed by adaptive changes antioxidant iron metabolism pathways macrophage phenotype polarization. When RBCs within Hp, potential deleterious are prevented. However, during hyper-hemolytic conditions or with chronic hemolysis, depleted readily distributes tissues where it might be exposed conditions. such conditions, ferric then accelerate tissue damage promoting peroxidative reactions activation inflammatory cascades. Hemopexin (Hx) another glycoprotein able bind high affinity. Hx sequesters inert, non-toxic form transports liver for catabolism excretion. present review we discuss components Hb/heme detoxification their therapeutic application wide hemolytic