CD163 (Cluster of Differentiation 163) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the CD163

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. CD163 is the high affinity scavenger receptor for the

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...

haptoglobin Haptoglobin (abbreviated as Hp) is the protein that in humans is encoded by the ''HP'' gene. In blood plasma, haptoglobin binds with high affinity to ''free'' hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidative ...

complex and in the absence of haptoglobin - with lower affinity - for hemoglobin alone. It also is a marker of cells from the

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

lineage. CD163 functions as innate immune sensor for

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and

gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

bacteria. The receptor was discovered in 1987.

Structure

The molecular size is 130

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

. 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 Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

., 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

, type 2

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

macrophage activation syndrome Macrophage activation syndrome is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis (SoJIA). In addition, MAS has bee ...

, Gaucher's disease,

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, HIV infection,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

and

Hodgkin Lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The conditio ...

. 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 A disintegrin and metalloprotease 17 (ADAM17), also called TACE (''tumor necrosis factor-α-converting enzyme''), is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases. Chemical characteristics ADAM17 ...

. Human CD163, but not mouse CD163, exhibits a strikingly higher affinity to

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 Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with

CSNK2B Casein kinase II subunit beta is a protein that in humans is encoded by the ''CSNK2B'' gene. This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcript ...

References

External links

* * {{Clusters of differentiation Clusters of differentiation