CD68

Last updated
CD68
Identifiers
Aliases CD68 , GP110, LAMP4, SCARD1, CD68 molecule
External IDs OMIM: 153634 MGI: 88342 HomoloGene: 955 GeneCards: CD68
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001251
NM_001040059

NM_001291058
NM_009853

RefSeq (protein)

NP_001035148
NP_001242

NP_001277987

Location (UCSC) Chr 17: 7.58 – 7.58 Mb Chr 11: 69.56 – 69.56 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
CD68 immunostaining demonstrating macrophages and giant cells in a case of xanthogranulomatous pyelonephritis Xanthogranulomatous pyelonephritis cd68.jpg
CD68 immunostaining demonstrating macrophages and giant cells in a case of xanthogranulomatous pyelonephritis

CD68 (Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). [5]

Contents

Structure and function

Human CD68 is a 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. [6] The human CD68 protein is encoded by the "CD68" gene which maps to Chromosome 17. [7] 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. [7] [8] The mouse equivalent is known as "macrosialin".

CD68 is functionally and evolutionarily related to other gene/protein family members, as follows: [6] [8] [9]

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. [10] [11]

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. [12]

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. [13] [14] [15] In this species, it is expressed in most macrophage populations and thus ED1 is commonly used as a pan-macrophage marker. [16] 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. [17]

See also

Related Research Articles

<span class="mw-page-title-main">CD32</span> Surface receptor glycoprotein

CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.

The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell. Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371.

<span class="mw-page-title-main">CD4</span> Marker on immune cells

In molecular biology, CD4 is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene.

<span class="mw-page-title-main">CD38</span> Protein-coding gene in the species Homo sapiens

CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling.

<span class="mw-page-title-main">CCL2</span>

For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.

<span class="mw-page-title-main">CD14</span>

CD14 is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).

<span class="mw-page-title-main">Integrin alpha M</span> Mammalian protein found in Homo sapiens

Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3). ITGAM is also known as CR3A, and cluster of differentiation molecule 11B (CD11B). The second chain of αMβ2 is the common integrin β2 subunit known as CD18, and integrin αMβ2 thus belongs to the β2 subfamily integrins.

<span class="mw-page-title-main">CD90</span> Mammalian protein found in Homo sapiens

Thy-1 or CD90 is a 25–37 kDa heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antigen. Thy-1 can be used as a marker for a variety of stem cells and for the axonal processes of mature neurons. Structural study of Thy-1 led to the foundation of the Immunoglobulin superfamily, of which it is the smallest member, and led to some of the initial biochemical description and characterization of a vertebrate GPI anchor and also the first demonstration of tissue specific differential glycosylation.

<span class="mw-page-title-main">CD33</span> Mammalian protein found in Homo sapiens

CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

<span class="mw-page-title-main">CD63</span>

CD63 antigen is a protein that, in humans, is encoded by the CD63 gene. CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

<span class="mw-page-title-main">CD69</span>

CD69 is a human transmembrane C-Type lectin protein encoded by the CD69 gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.

4F2 cell-surface antigen heavy chain Protein-coding gene in the species Homo sapiens

4F2 cell-surface antigen heavy chain is a protein that in humans is encoded by the SLC3A2 gene.

<span class="mw-page-title-main">CD47</span> Protein-coding gene in humans

CD47 also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a don't eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis.

<span class="mw-page-title-main">LAMP1</span>

Lysosomal-associated membrane protein 1 (LAMP-1) also known as lysosome-associated membrane glycoprotein 1 and CD107a, is a protein that in humans is encoded by the LAMP1 gene. The human LAMP1 gene is located on the long arm (q) of chromosome 13 at region 3, band 4 (13q34).

<span class="mw-page-title-main">CD48</span> Mammalian protein found in Homo sapiens

CD48 antigen also known as B-lymphocyte activation marker (BLAST-1) or signaling lymphocytic activation molecule 2 (SLAMF2) is a protein that in humans is encoded by the CD48 gene.

<span class="mw-page-title-main">CD200</span>

OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene.

<span class="mw-page-title-main">LAMP3</span>

Lysosome-associated membrane glycoprotein 3 is a protein that in humans is encoded by the LAMP3 gene. It is one of the lysosome-associated membrane glycoproteins.

<span class="mw-page-title-main">CD 205</span>

CD205 also called Lymphocyte antigen 75 is a protein that in humans is encoded by the LY75 gene.

TREM2 Protein-coding gene in the species Homo sapiens

Triggering receptor expressed on myeloid cells 2(TREM2) is a protein that in humans is encoded by the TREM2 gene. TREM2 is expressed on macrophages, immature monocyte-derived dendritic cells, osteoclasts, and microglia, which are immune cells in the central nervous system. In the liver, TREM2 is expressed by several cell types, including macrophages, that respond to injury. In the intestine, TREM2 is expressed by myeloid-derived dendritic cells and macrophage. TREM2 is overexpressed in many tumor types and has anti-inflammatory activities. It might therefore be a good therapeutic target.

CLEC12A Protein-coding gene in humans

C-type lectin domain family 12 member A is a protein that in humans is encoded by the CLEC12A gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129226 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018774 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Holness CL, Simmons DL (March 1993). "Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins". Blood. 81 (6): 1607–13. doi: 10.1182/blood.V81.6.1607.1607 . PMID   7680921.
  6. 1 2 "CD68 - Macrosialin precursor - Homo sapiens (Human) - CD68 gene & protein". www.uniprot.org. Retrieved 16 September 2017.
  7. 1 2 "CD68 Symbol Report". www.genenames.org. Retrieved 16 September 2017.
  8. 1 2 "CD68 Gene - CD68 Protein - CD68 Antibody". www.genecards.org. Retrieved 16 September 2017.
  9. "MACROPHAGE ANTIGEN CD68; CD68". omim.org. Retrieved 16 September 2017.
  10. Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 135–136. ISBN   1-84110-100-1.
  11. Manduch M, Dexter DF, Jalink DW, Vanner SJ, Hurlbut DJ (January 2009). "Undifferentiated pancreatic carcinoma with osteoclast-like giant cells: report of a case with osteochondroid differentiation". Pathology, Research and Practice. 205 (5): 353–9. doi:10.1016/j.prp.2008.11.006. PMID   19147301.
  12. "Product Overview: anti-CD68 Antibodies". www.antibodies-online.com. Retrieved 14 September 2017.
  13. Dijkstra CD, Döpp EA, Joling P, Kraal G (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. 54 (3): 589–99. PMC   1453512 . PMID   3882559.
  14. Gomes LF, Lorente S, Simon-Giavarotti KA, Areco KN, Araújo-Peres C, Videla LA (2004). "Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations". Molecular Aspects of Medicine. 25 (1–2): 183–90. doi:10.1016/j.mam.2004.02.018. PMID   15051326.
  15. Xie R, Kuijpers-Jagtman AM, Maltha JC (February 2009). "Osteoclast differentiation and recruitment during early stages of experimental tooth movement in rats". European Journal of Oral Sciences. 117 (1): 43–50. doi:10.1111/j.1600-0722.2008.00588.x. PMID   19196317.
  16. Damoiseaux JG, Döpp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (September 1994). "Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1". Immunology. 83 (1): 140–7. PMC   1415006 . PMID   7821959.
  17. Vincent PA, Rebres RA, Lewis EP, Hurst V, Saba TM (November 1993). "Release of ED1 fibronectin from matrix of perfused lungs after vascular injury is independent of protein synthesis". The American Journal of Physiology. 265 (5 Pt 1): L485-92. doi:10.1152/ajplung.1993.265.5.L485. PMID   8238536.

Further reading