Overview of the receptor pathways for endocytosis of extracellular heme and hemoglobin in complex with hemopexin and haptoglobin, respectively. LRP/CD91 and CD163 represent 2 pathways for uptake of extracellular heme incorporated in Hx-heme and haptoglobin-hemoglobin. Both receptors are highly expressed in phagocytic macrophages, which are known to metabolize heme into bilirubin, Fe, and carbon monoxide. In addition to the expression in macrophages, LRP/CD91 is highly expressed in several other cell types including hepatocytes, neurons, and syncytiotrophoblasts.³¹