Biology:CD68

From HandWiki
Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
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).[1]

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.[2] The human CD68 protein is encoded by the "CD68" gene which maps to Chromosome 17.[3] 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.[3][4] The mouse equivalent is known as "macrosialin".

CD68 is functionally and evolutionarily related to other gene/protein family members, including:[2][4][5]

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.[6][7]

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.[8]

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.[9][10][11] In this species, it is expressed in most macrophage populations and thus ED1 is commonly used as a pan-macrophage marker.[12] 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.[13]

See also

References

  1. "Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins". Blood 81 (6): 1607–13. March 1993. doi:10.1182/blood.V81.6.1607.1607. PMID 7680921. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=7680921. 
  2. 2.0 2.1 "CD68 - Macrosialin precursor - Homo sapiens (Human) - CD68 gene & protein" (in en). https://www.uniprot.org/uniprot/P34810. 
  3. 3.0 3.1 "CD68 Symbol Report". https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=1693. 
  4. 4.0 4.1 "CD68 Gene - CD68 Protein - CD68 Antibody". https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD68. 
  5. "MACROPHAGE ANTIGEN CD68; CD68" (in en-us). http://omim.org/entry/153634. 
  6. 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. 
  7. "Undifferentiated pancreatic carcinoma with osteoclast-like giant cells: report of a case with osteochondroid differentiation". Pathology, Research and Practice 205 (5): 353–9. January 2009. doi:10.1016/j.prp.2008.11.006. PMID 19147301. 
  8. "Product Overview: anti-CD68 Antibodies" (in en). http://www.antibodies-online.com/abstract/CD68+Molecule+(CD68)+Antibody/. 
  9. "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. March 1985. PMID 3882559. 
  10. "Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations". Molecular Aspects of Medicine 25 (1–2): 183–90. 2004. doi:10.1016/j.mam.2004.02.018. PMID 15051326. 
  11. "Osteoclast differentiation and recruitment during early stages of experimental tooth movement in rats". European Journal of Oral Sciences 117 (1): 43–50. February 2009. doi:10.1111/j.1600-0722.2008.00588.x. PMID 19196317. https://research.rug.nl/en/publications/osteoclast-differentiation-and-recruitment-during-early-stages-of-experimental-tooth-movement-in-rats(cb6c36a8-e0d3-433b-a5cc-cb611fe02c79).html. 
  12. "Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1". Immunology 83 (1): 140–7. September 1994. PMID 7821959. 
  13. "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. November 1993. doi:10.1152/ajplung.1993.265.5.L485. PMID 8238536. 

Further reading

  • Human Gene Database: GeneCards CD68
  • UniProt Knowledgebase (CD68_HUMAN)
  • "Cellular distribution and contribution of cyclooxygenase COX-2 to diabetogenesis in NOD mouse". Cell and Tissue Research 310 (2): 169–75. November 2002. doi:10.1007/s00441-002-0628-6. PMID 12397372. 
  • "Multiple Ets factors and interferon regulatory factor-4 modulate CD68 expression in a cell type-specific manner". The Journal of Biological Chemistry 278 (24): 21909–19. June 2003. doi:10.1074/jbc.M212150200. PMID 12676954. 
  • "Granular cell tumor: immunohistochemical assessment of inhibin-alpha, protein gene product 9.5, S100 protein, CD68, and Ki-67 proliferative index with clinical correlation". Archives of Pathology & Laboratory Medicine 128 (7): 771–5. July 2004. doi:10.5858/2004-128-771-GCTIAO. PMID 15214825. 
  • "Macrophage/histiocytic antigen CD68 expression in neoplastic and reactive lymph nodes". Roczniki Akademii Medycznej W Bialymstoku 49 (Suppl 1): 73–5. 2004. PMID 15638380. 
  • "[The "classical" macrophage marker CD68 is strongly expressed in primary human fibroblasts]" (in de). Verhandlungen der Deutschen Gesellschaft für Pathologie 87: 215–23. 2003. PMID 16888915. 
  • "Distribution of CD14+ and CD68+ macrophages in the placental bed and basal plate of women with preeclampsia and preterm labor". Placenta 28 (5–6): 571–6. 2007. doi:10.1016/j.placenta.2006.07.007. PMID 17052752. 
  • "Cell-type-specific expression of the human CD68 gene is associated with changes in Pol II phosphorylation and short-range intrachromosomal gene looping". Genomics 90 (3): 407–15. September 2007. doi:10.1016/j.ygeno.2007.04.010. PMID 17583472. 
  • "Prognostic significance of macrophage infiltration in leiomyosarcomas". Clinical Cancer Research 14 (5): 1423–30. March 2008. doi:10.1158/1078-0432.CCR-07-1712. PMID 18316565. 
  • "Immunohistological features of hip synovitis in ankylosing spondylitis with advanced hip involvement". Scandinavian Journal of Rheumatology 38 (2): 154–5. 2009. doi:10.1080/03009740802409504. PMID 19165649.