FIG. 2.

CD163-mediated scavenging of Hb upon intravascular hemolysis. CD163 is highly expressed on phagocytic macrophages. Upon hemolysis, released hemoglobin (Hb) is rapidly bound by the acute-phase protein Hp forming the haptoglobin–hemoglobin (Hp-Hb) complex. The complex is subsequently bound and removed from the circulation by CD163-positive macrophages in the liver, spleen,and bone marrow. The uptake of Hb by macrophages contributes to the recycling of iron and also to the inflammatory response. The uptake of Hb in macrophages and subsequent degradation of heme by heme oxygenase-1 (HO-1), produce the anti-inflammatory metabolites, Fe²⁺, CO, and biliverdin. Biliverdin reductase converts biliverdin to bilirubin, which is secreted to the cell exterior. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars.