Natural History of the Bruise: Formation, Elimination, and Biological Effects of Oxidized Hemoglobin
Figure 1
Schematic representation of hemoglobin oxidation and the different biological effects of oxidized Hb species. Hb is released from red blood cells following intra- or extravascular hemolysis. Hb can undergo spontaneous oxidation, or, alternatively, nitric oxide (NO) can trigger Hb oxidation to MetHb. Peroxidation of Hb and MetHb by H2O2 or lipid hydroperoxides (LOOH) leads to the formation of ferrylHb, that is, a mixture of globin radicals, porphyrin radicals, and covalently cross-linked Hb multimers. Haptoglobin (Hp) binds extracellular Hb and facilitates its internalization by macrophages. MetHb and ferrylHb can release heme and induce oxidative modification of lipids such as low-density lipoprotein (LDL), sensitizing cells to oxidant-mediated killing. FerrylHb is a proinflammatory agonist that targets endothelial cells. Heme release from oxidized Hb species and peroxidation of Hb are partially inhibited by Hp.
