CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in 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 ...

lineage (e.g., monocytic

phagocyte Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

s), by circulating macrophages, and by tissue macrophages (e.g.,

Kupffer cell Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Ku ...

s, microglia).

Structure and function

Human CD68 is a Type I

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

glycoprotein, heavily

glycosylated Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

in its extracellular domain, with a molecular weight of 110 kD. Its primary sequence consists of 354 amino acids with predicted molecular weight of 37.4 kD if it were not glycosylated. The human CD68 protein is encoded by the "CD68" gene which maps to

Chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

. Other names or aliases for this gene in humans and other animals include: CD68 Molecule, CD68 Antigen, GP110, Macrosialin, Scavenger Receptor Class D, Member 1, SCARD1, and LAMP4. The mouse equivalent is known as "macrosialin". CD68 is functionally and evolutionarily related to other gene/protein family members, including: * the hematopoietic mucin-like family of molecules that includes leukosialin/

CD43 Leukosialin also known as sialophorin or CD43 (cluster of differentiation 43) is a transmembrane cell surface protein that in humans is encoded by the ''SPN'' (sialophorin) gene. Function Sialophorin (leukosialin) is a major sialoglycoprotein ...

and stem cell antigen

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

; * the

Lysosome-associated membrane glycoprotein Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal d ...

(LAMP) family (CD68 localizes primarily to

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...

s and

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

s, but with a smaller fraction circulating to the cell surface); * the scavenger receptor family, whose members typically function to clear cellular debris, promote

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

, and mediate the recruitment and activation of macrophages.

Use in pathology and research

Immunohistochemistry can be used to identify the presence of CD68, which is found in the cytoplasmic granules of a range of different blood cells and myocytes. It is particularly useful as a marker for the various cells of the macrophage lineage, including

histiocytes A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...

giant cell A giant cell (also known as multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. Although there is typically a focus on the pathologica ...

Kupffer cells Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Ku ...

, and

s. This allows it to be used to distinguish diseases of otherwise similar appearance, such as the monocyte/macrophage and lymphoid forms of

leukaemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

(the latter being CD68 negative). Its presence in macrophages also makes it useful in diagnosing conditions related to proliferation or abnormality of these cells, such as

malignant histiocytosis Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histio ...

, histiocytic

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

, and

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 ...

. Anti-CD68 monoclonal antibodies that react with tissues of rodent and other species include ED1, FA-11, KP1 (a.k.a. C68/684), 6A326, 6F3, 12E2, 10B1909, and SPM130. Monoclonals that react with humans include, Ki-M7, PG-M1, 514H12, ABM53F5, 3F7C6, 3F7D3, Y1/82A, EPR20545, CDLA68-1, LAMP4-824.

ED1

ED1 is the most widely used monoclonal antibody clone directed against the rat CD68 protein and is used to identify macrophages, Kupffer cells, osteoclasts, monocytes, and activated microglia in rat tissues. In this species, it is expressed in most macrophage populations and thus ED1 is commonly used as a pan-macrophage marker. However, in some cell types it is detectable only when up-regulated, such as activated but not quiescent microglia, and can thus be used as a marker of inflammatory conditions and immune reactions in those instances. Commercial suppliers report that ED1 is used for detection of the CD68 protein by immunohistochemical staining, flow cytometry, and western blot methods and that in addition to rat it cross-reacts with

bovine Bovines (subfamily Bovinae) comprise a diverse group of 10 genera of medium to large-sized ungulates, including cattle, bison, African buffalo, water buffalos, and the four-horned and spiral-horned antelopes. The evolutionary relationship betwe ...

species. The ED1 anti-CD68 antibody is not to be confused with the fibronectin extra domain ED1.

Structure and function

Use in pathology and research

ED1

See also

References

Further reading