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ICAM3
Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50 (Cluster of Differentiation 50), is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

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Protein structure

ICAM3 is a 110–160 kDa protein that belongs to the intercellular adhesion molecule (ICAM) family.10 Like the other proteins in this family, ICAM3 is a type I transmembrane glycoprotein and consists in part of a hydrophobic transmembrane domain and a short domain that extends into the cytoplasm.11 ICAM3 also contains five extracellular immunoglobulin domains.12

Function

ICAM3 is found on the surface of leukocytes, and the ICAM3 gene is constitutively expressed in these cells.13 Interactions between ICAM3 and specific integrin receptors facilitate adhesion between cells.14

Dendritic and T cell binding

ICAM3 has an important function in the immune cell response, as it helps facilitate initial interactions between T cells and dendritic cells.15 Resting T cells show high levels of ICAM3 expression.16 ICAM3 on these T cells can bind to DC-SIGN, a transmembrane receptor present on dendritic cells, creating temporary contact between resting T cells and dendritic cells.1718 This adhesion allows the T cell receptor (TCR) to interact with major histocompatibility complex (MHC) molecules on the surface of the dendritic cell, which, upon binding between the TCR, the MHC, and the peptide coupled to the MHC, facilitates T cell activation.192021

Apoptosis

ICAM3 plays a role in apoptotic cell clearance by promoting the movement of macrophages, which ingest and break down unhealthy cells via phagocytosis, to cells undergoing apoptosis.22 Apoptotic cells can release extracellular vesicles containing ICAM3, which acts as a chemoattractant to phagocytes such as macrophages, directing them toward apoptotic cells.2324 Apoptotic cells also contain altered ICAM3 proteins on their surface.25 These altered proteins allow macrophages to specifically target and bind apoptotic cells.26 This process is believed to involve binding between ICAM3 and CD14 receptors, which are a type of cell surface receptor expressed on macrophages and other phagocytes.2728

Mast cells

ICAM3 is also found on mast cells, another type of leukocyte.29 Mast cells taken from human lungs and the HMC-1 line, a human mast cell line, both showed expression of ICAM3.30 ICAM3 helps mediate the adhesion of mast cells to the extracellular matrix.31

Interactions

Dendritic and T cell binding

Binding between ICAM3 and DC-SIGN, which takes place during initial interactions between T cells and dendritic cells, occurs with high affinity.323334 This binding process is also calcium-dependent.353637

Apoptosis

CD14, a receptor expressed on the surface of phagocytes, can also bind ICAM3.3839 Interactions between CD14 and altered ICAM3 molecules on apoptotic cells are believed to help promote phagocytosis of apoptotic cells.4041

Integrins

ICAM3 is a known ligand for LFA-1, an integrin expressed by leukocytes.42 To facilitate binding, the I domain of LFA-1 interacts with the ICAM3 protein’s first immunoglobulin domain.43 ICAM3 also binds the integrin αDβ2.44

Additional interactions

ICAM3 has been shown to interact with activated ERM proteins, including ezrin (EZR) and moesin, in T cells.45

See also

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

References

  1. "ICAM3 intercellular adhesion molecule 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-03-10. https://www.ncbi.nlm.nih.gov/gene/3385

  2. Xiao X, Mruk DD, Cheng CY (March 2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update. 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576004

  3. Pastwińska J, Żelechowska P, Walczak-Drzewiecka A, Brzezińska-Błaszczyk E, Dastych J (December 2020). "The Art of Mast Cell Adhesion". Cells. 9 (12): 2664. doi:10.3390/cells9122664. PMC 7764012. PMID 33322506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764012

  4. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  5. Svajger U, Anderluh M, Jeras M, Obermajer N (October 2010). "C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity". Cellular Signalling. 22 (10): 1397–1405. doi:10.1016/j.cellsig.2010.03.018. PMC 7127357. PMID 20363321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127357

  6. Gupta RK, Gupta GS (2012), Gupta GS (ed.), "Dendritic Cell Lectin Receptors (Dectin-2 Receptors Family)", Animal Lectins: Form, Function and Clinical Applications, Vienna: Springer, pp. 749–771, doi:10.1007/978-3-7091-1065-2_35, ISBN 978-3-7091-1065-2, retrieved 2022-03-11 978-3-7091-1065-2

  7. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  8. Numata Y, Hirayama D, Wagatsuma K, Iida T, Nakase H (2018), Turksen K (ed.), "Apoptotic Cell Clearance in Gut Tissue: Role of Intestinal Regeneration", Autophagy in Health and Disease: Potential Therapeutic Approaches, Stem Cell Biology and Regenerative Medicine, Cham: Springer International Publishing, pp. 87–100, doi:10.1007/978-3-319-98146-8_6, ISBN 978-3-319-98146-8, retrieved 2022-03-09 978-3-319-98146-8

  9. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  10. Xiao X, Mruk DD, Cheng CY (March 2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update. 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576004

  11. Smith CW (February 2008). "3. Adhesion molecules and receptors". The Journal of Allergy and Clinical Immunology. 2008 Mini-Primer on Allergic and Immunologic Diseases. 121 (2 Suppl): S375-9, quiz S414. doi:10.1016/j.jaci.2007.07.030. PMID 18241685. https://doi.org/10.1016%2Fj.jaci.2007.07.030

  12. Smith CW (February 2008). "3. Adhesion molecules and receptors". The Journal of Allergy and Clinical Immunology. 2008 Mini-Primer on Allergic and Immunologic Diseases. 121 (2 Suppl): S375-9, quiz S414. doi:10.1016/j.jaci.2007.07.030. PMID 18241685. https://doi.org/10.1016%2Fj.jaci.2007.07.030

  13. Xiao X, Mruk DD, Cheng CY (March 2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update. 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576004

  14. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  15. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  16. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  17. Svajger U, Anderluh M, Jeras M, Obermajer N (October 2010). "C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity". Cellular Signalling. 22 (10): 1397–1405. doi:10.1016/j.cellsig.2010.03.018. PMC 7127357. PMID 20363321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127357

  18. Gupta RK, Gupta GS (2012), Gupta GS (ed.), "Dendritic Cell Lectin Receptors (Dectin-2 Receptors Family)", Animal Lectins: Form, Function and Clinical Applications, Vienna: Springer, pp. 749–771, doi:10.1007/978-3-7091-1065-2_35, ISBN 978-3-7091-1065-2, retrieved 2022-03-11 978-3-7091-1065-2

  19. Svajger U, Anderluh M, Jeras M, Obermajer N (October 2010). "C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity". Cellular Signalling. 22 (10): 1397–1405. doi:10.1016/j.cellsig.2010.03.018. PMC 7127357. PMID 20363321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127357

  20. Gupta RK, Gupta GS (2012), Gupta GS (ed.), "Dendritic Cell Lectin Receptors (Dectin-2 Receptors Family)", Animal Lectins: Form, Function and Clinical Applications, Vienna: Springer, pp. 749–771, doi:10.1007/978-3-7091-1065-2_35, ISBN 978-3-7091-1065-2, retrieved 2022-03-11 978-3-7091-1065-2

  21. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  22. Numata Y, Hirayama D, Wagatsuma K, Iida T, Nakase H (2018), Turksen K (ed.), "Apoptotic Cell Clearance in Gut Tissue: Role of Intestinal Regeneration", Autophagy in Health and Disease: Potential Therapeutic Approaches, Stem Cell Biology and Regenerative Medicine, Cham: Springer International Publishing, pp. 87–100, doi:10.1007/978-3-319-98146-8_6, ISBN 978-3-319-98146-8, retrieved 2022-03-09 978-3-319-98146-8

  23. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  24. Hawkins LA, Devitt A (January 2013). "Current understanding of the mechanisms for clearance of apoptotic cells-a fine balance". Journal of Cell Death. 6: 57–68. doi:10.4137/jcd.s11037. PMC 4147779. PMID 25278779. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147779

  25. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  26. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  27. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  28. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  29. Pastwińska J, Żelechowska P, Walczak-Drzewiecka A, Brzezińska-Błaszczyk E, Dastych J (December 2020). "The Art of Mast Cell Adhesion". Cells. 9 (12): 2664. doi:10.3390/cells9122664. PMC 7764012. PMID 33322506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764012

  30. Pastwińska J, Żelechowska P, Walczak-Drzewiecka A, Brzezińska-Błaszczyk E, Dastych J (December 2020). "The Art of Mast Cell Adhesion". Cells. 9 (12): 2664. doi:10.3390/cells9122664. PMC 7764012. PMID 33322506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764012

  31. Pastwińska J, Żelechowska P, Walczak-Drzewiecka A, Brzezińska-Błaszczyk E, Dastych J (December 2020). "The Art of Mast Cell Adhesion". Cells. 9 (12): 2664. doi:10.3390/cells9122664. PMC 7764012. PMID 33322506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764012

  32. Svajger U, Anderluh M, Jeras M, Obermajer N (October 2010). "C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity". Cellular Signalling. 22 (10): 1397–1405. doi:10.1016/j.cellsig.2010.03.018. PMC 7127357. PMID 20363321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127357

  33. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  34. Rahimi N (2020-12-22). "C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors". Biology. 10 (1): 1. doi:10.3390/biology10010001. ISSN 2079-7737. PMC 7822156. PMID 33375175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822156

  35. Svajger U, Anderluh M, Jeras M, Obermajer N (October 2010). "C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity". Cellular Signalling. 22 (10): 1397–1405. doi:10.1016/j.cellsig.2010.03.018. PMC 7127357. PMID 20363321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127357

  36. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  37. Rahimi N (2020-12-22). "C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors". Biology. 10 (1): 1. doi:10.3390/biology10010001. ISSN 2079-7737. PMC 7822156. PMID 33375175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822156

  38. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  39. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  40. Cockram TO, Dundee JM, Popescu AS, Brown GC (2021). "The Phagocytic Code Regulating Phagocytosis of Mammalian Cells". Frontiers in Immunology. 12: 629979. doi:10.3389/fimmu.2021.629979. ISSN 1664-3224. PMC 8220072. PMID 34177884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220072

  41. Marek CJ, Erwig LP (2009), Dong Z, Yin XM (eds.), "Clearance of Apoptotic Cells – Mechanisms and Consequences", Essentials of Apoptosis: A Guide for Basic and Clinical Research, Totowa, NJ: Humana Press, pp. 261–282, doi:10.1007/978-1-60327-381-7_11, ISBN 978-1-60327-381-7, retrieved 2022-03-09 978-1-60327-381-7

  42. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  43. van Kooyk Y, Geijtenbeek TB (August 2002). "A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions". Immunological Reviews. 186: 47–56. doi:10.1034/j.1600-065x.2002.18605.x. PMID 12234361. S2CID 23267228. /wiki/Doi_(identifier)

  44. Smith CW (February 2008). "3. Adhesion molecules and receptors". The Journal of Allergy and Clinical Immunology. 2008 Mini-Primer on Allergic and Immunologic Diseases. 121 (2 Suppl): S375-9, quiz S414. doi:10.1016/j.jaci.2007.07.030. PMID 18241685. https://doi.org/10.1016%2Fj.jaci.2007.07.030

  45. Cornely R, Grewal T, Gaus K (2012), Kavallaris M (ed.), "The Actin Cytoskeleton and Membrane Organisation in T Lymphocytes", Cytoskeleton and Human Disease, Totowa, NJ: Humana Press, pp. 103–121, doi:10.1007/978-1-61779-788-0_5, ISBN 978-1-61779-788-0, retrieved 2022-03-09 978-1-61779-788-0