CD68

Structure and function

Human CD68 is a Type I transmembrane glycoprotein, heavily glycosylated 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. 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 and stem cell antigen CD34;
• the lysosome-associated membrane glycoprotein (LAMP) family (CD68 localizes primarily to lysosomes and endosomes, but with a smaller fraction circulating to the cell surface);
• the scavenger receptor family, whose members typically function to clear cellular debris, promote phagocytosis, 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 monocytes, histiocytes, giant cells, Kupffer cells, and osteoclasts. This allows it to be used to distinguish diseases of otherwise similar appearance, such as the monocyte/macrophage and lymphoid forms of leukaemia (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, histiocytic lymphoma, and Gaucher's disease.

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 species.

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

References

References

1. (March 1993). "Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins". Blood.
2. "CD68 - Macrosialin precursor - Homo sapiens (Human) - CD68 gene & protein".
3. "CD68 Symbol Report".
4. "CD68 Gene - CD68 Protein - CD68 Antibody".
5. "MACROPHAGE ANTIGEN CD68; CD68".
6. Leong, Anthony S-Y. (2003). "Manual of Diagnostic Cytology". Greenwich Medical Media, Ltd..
7. (January 2009). "Undifferentiated pancreatic carcinoma with osteoclast-like giant cells: report of a case with osteochondroid differentiation". Pathology, Research and Practice.
8. "Product Overview: anti-CD68 Antibodies".
9. (March 1985). "The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3". Immunology.
10. (2004). "Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations". Molecular Aspects of Medicine.
11. (February 2009). "Osteoclast differentiation and recruitment during early stages of experimental tooth movement in rats". European Journal of Oral Sciences.
12. (September 1994). "Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1". Immunology.
13. (November 1993). "Release of ED1 fibronectin from matrix of perfused lungs after vascular injury is independent of protein synthesis". The American Journal of Physiology.