CD163
CD163 (Cluster of Differentiation 163) is a protein that in humans is encoded by the CD163 gene. CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex and in the absence of haptoglobin - with lower affinity - for hemoglobin alone. It also is a marker of cells from the monocyte/macrophage lineage. CD163 functions as innate immune sensor for gram-positive and gram-negative bacteria. The receptor was discovered in 1987. Structure. The molecular size is 130 kDa. The receptor belongs to the scavenger receptor cysteine rich family type B and consists of a 1048 amino acid residues  extracellular domain, a single transmembrane segment and a cytoplasmic tail with several splice variants. Clinical significance. A soluble form of the receptor exists in plasma, and cerebrospinal fluid., commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor, which may represent a form of modulation of CD163 function. sCD163 shedding occurs as a result of enzymatic cleavage by ADAM17. sCD163 is upregulated in a large range of inflammatory diseases including liver cirrhosis, type 2 diabetes, macrophage activation syndrome, Gaucher's disease, sepsis, HIV infection, rheumatoid arthritis and Hodgkin Lymphoma. sCD163 is also upregulated in cerebrospinal fluid  after subarachnoid haemorrhage. CD163 has recently been identified as expressed on neurons in the CNS following hemorrhage, although the significance of this is unclear. The excretion of soluble CD163 into the urine is tightly associated with the presence of active glomerulonephritis in systemic lupus erythematosus and ANCA vasculitis and can be used to track response to therapy. Differences between mouse and human. Differences between mice and humans in CD163 biology are important to note since preclinical studies are frequently conducted in mice. sCD163 shedding occurs in humans but not mice, due to the emergence of an Arg-Ser-Ser-Arg  sequence in humans, essential for enzymatic cleavage by ADAM17. Human CD163, but mouse CD163, exhibits a strikingly higher affinity to hemoglobin-haptoglobin complex compared to hemoglobin alone. Animal studies. Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes Porcine Reproductive and Respiratory Syndrome. Interactions. CD163 has been shown to interact with CSNK2B.