Several antibodies to an unknown monocyte/macrophage-specific antigen were described in the 1980s and 1990s, leading to the CD163 designation at the 6th Leukocyte Typing Workshop in 1996. The principal function of this membrane-bound protein as a monocyte/macrophage-specific scavenger receptor for haemoglobin-haptoglobin complexes was described in 2001, and soon after it was realized that relatively high concentrations of a soluble form of the receptor are present in the circulation (soluble CD163, sCD163).
The soluble form probably functions as part of the innate immune defence by reversibly binding bacteria and free haemoglobin in the circulation for further processing by the immune system. However, due to the high and specific expression on macrophages, sCD163 has gained much attention as a potential biomarker reflecting macrophage activation in inflammatory conditions.