Involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1 (By similarity). After shedding, the soluble form (sCD163) may play an anti-inflammatory role. Interacts with CSNK2B. Expressed in monocytes and mature macrophages such as Kupffer cells in the liver, red pulp macrophages in the spleen and mesenteric lymph nodes. Induced by anti-inflammatory mediators such as glucocorticoids and IL10; suppressed by IL4. The SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes. A soluble form (sCD163) is produced by proteolytic shedding which can be induced by lipopolysaccharide, phorbol ester and Fc region of immunoglobulin gamma. This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound metalloproteinases ADAMs (By similarity).