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CD163 (Cluster of Differentiation 163) is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the CD163
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. CD163 is the high affinity scavenger receptor for the
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. 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 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 monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
/
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
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. The Gram stain is ...
and
gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
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 Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
., 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, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
, type 2
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, macrophage activation syndrome,
Gaucher's disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low ...
,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
,
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
infection,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
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 lymph nodes. The condition was named a ...
. sCD163 is also upregulated in cerebrospinal fluid after
subarachnoid haemorrhage Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of c ...
. CD163 has recently been identified as expressed on
neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s 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 Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...
in
systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...
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, activated by substrate presentatio ...
. Human CD163, but not mouse CD163, exhibits a strikingly higher affinity to
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. 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.


See also

*
Cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...


References


Further reading

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External links

* * {{Clusters of differentiation Clusters of differentiation