Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Alvaro Torres-HuertaEmail author
  • Estefania Aleman-Navarro
  • Maria Elena Bravo-Adame
  • Monserrat Alba Sandoval-Hernandez
  • Oscar Arturo Migueles-Lozano
  • Yvonne Rosenstein
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_523


Historical Background

CD43, also called sialophorin or leukosialin, was first identified as a defective molecule of leukocytes and platelets of patients affected with the Wiskott–Aldrich syndrome, yet the molecule responsible for this immunodeficiency turned out to be WASP. It was thought that expression of this heavily glycosylated, mucin-type membrane protein was restricted to hematopoietic cells. However, recent advances in the field evidence that CD43 is present in non-lymphoid tissues, particularly tumor cells. Here we reviewed the most important features about this molecule, highlighting the recent advances that have contributed to our understanding of the roles of CD43.

Gene Expression and Protein Structure

CD43 is a type I cell surface glycoprotein abundantly expressed on almost all hematopoietic cells, except for erythrocytes and resting B cells. Although initially considered an immune cell molecule, recent reports...

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  1. Aguilar-Delfin I, Fierro NA, Rosenstein Y. CD43. UCSD-nature molecule pages. 2006. doi:10.1038/mp.a000001.01.CrossRefGoogle Scholar
  2. Alkhamesi NA, Roberts G, Ziprin P, Peck DH. Induction of proteases in peritoneal carcinomatosis, the role of ICAM-1/CD43 interaction. Biomark Insights. 2007;2:377–84.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Allenspach EJ, Cullinan P, Tong J, Tang Q, Tesciuba AG, Cannon JL, et al. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity. 2001;15(5):739–50.PubMedCrossRefGoogle Scholar
  4. Amano J, Morimoto C, Irimura T. Intestinal epithelial cells express and secrete the CD43 glycoform that contains core 2 O-glycans. Microbes Infect. 2001;3(9):723–8.PubMedCrossRefGoogle Scholar
  5. Andersson CX, Fernandez-Rodriguez J, Laos S, Sikut R, Sikut A, Baeckstrom D, Hansson GC. CD43 has a functional NLS, interacts with beta-catenin, and affects gene expression. Biochem Biophys Res Commun. 2004;316(1):12–7.PubMedCrossRefGoogle Scholar
  6. Andersson CX, Fernandez-Rodriguez J, Laos S, Baeckstrom D, Haass C, Hansson GC. Shedding and γ-secretase-mediated intramembrane proteolysis of the mucin-type molecule CD43. Biochem J. 2005;387(Pt 2):377–84.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Balikova A, Jääger K, Viil J, Maimets T, Kadaja-Saarepuu L. Leukocyte marker CD43 promotes cell growth in co-operation with β-catenin in non-hematopoietic cancer cells. Int J Oncol. 2012;41(1):299–309.PubMedPubMedCentralGoogle Scholar
  8. Barat C, Tremblay MJ. Engagement of CD43 enhances human immunodeficiency virus type 1 transcriptional activity and virus production that is induced upon TCR/CD3 stimulation. J Biol Chem. 2002;277(32):28714–28724. Epub 2002 Jun 3.PubMedCrossRefGoogle Scholar
  9. Bravo-Adame ME, Vera-Estrella R, Barkla BJ, Martínez-Campos C, Flores-Alcantar A, Ocelotl-Oviedo JP, et al. An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes. Immunology. 2016. doi:10.1111/imm.12670.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Camacho-Concha N, Olivos-Ortiz A, Nuñez-Rivera A, Pedroza-Saavedra A, Gutierrez-Xicotencatl L, Rosenstein Y, et al. CD43 promotes cells transformation by preventing Merlin-mediated contact inhibition of growth. PLoS One. 2013;8(11):e80806. doi:10.1371/journal.pone.0080806. eCollection 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Campo M, Randhawa AK, Dunstan S, Farrar J, Caws M, Bang ND, et al. Common polymorphisms in the CD43 gene region are associated with tuberculosis disease and mortality. Am J Respir Cell Mol Biol. 2015;52(3):342–8. doi:10.1165/rcmb.2014-0114OC.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Ford ML, Onami TM, Sperling AI, Ahmed R, Evavold BD. CD43 modulates severity and onset of experimental autoimmune encephalomyelitis. J Immunol. 2003;171(12):6527–33.PubMedCrossRefGoogle Scholar
  13. Fratazzi C, Manjunath N, Arbeit RD, Carini C, Gerken TA, Ardman B, et al. A macrophage invasion mechanism for mycobacteria implicating the extracellular domain of CD43. J Exp Med. 2000;192(2):183–92.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Freire-de-Lima L, Alisson-Silva F, Carvalho ST, Takiya CM, Rodrigues MM, DosReis GA, et al. Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses. J Biol Chem. 2010;285(18):13388–96.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Fu Q, Cash SE, Andersen JJ, Kennedy CR, Oldenburg DG, Zander VB, et al. CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target. Int J Cancer. 2013;132(8):1761–70. doi:10.1002/ijc.27873. Epub 2012 Oct 29.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Fukuda M. Roles of mucin-type O-glycans in cell adhesion. Biochim Biophys Acta. 2002;1573(3):394–405.PubMedCrossRefGoogle Scholar
  17. Fulcher JA, Chang MH, Wang S, Almazan T, Hashimi ST, Eriksson AU, et al. Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. J Biol Chem. 2009;284(39):26860–70.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Galindo-Albarrán AO, Ramírez-Pliego O, Labastida-Conde RG, Melchy-Pérez EI, Liquitaya-Montiel A, Esquivel-Guadarrama FR, et al. CD43 signals prepare human T cells to receive cytokine differentiation signals. J Cell Physiol. 2014;229(2):172–80.PubMedCrossRefGoogle Scholar
  19. Hartshorn KL, White MR. Influenza A virus up-regulates neutrophil adhesion molecules and adhesion to biological surfaces. J Leukoc Biol. 1999;65(5):614–22.PubMedCrossRefGoogle Scholar
  20. Hasegawa K, Tanaka S, Fujiki F, Morimoto S, Nakano K, Kinoshita H, et al. Glycosylation status of CD43 protein is associated with resistance of leukemia cells to CTL-mediated cytolysis. PLoS One. 2016;11(3):e0152326. doi:10.1371/journal.pone.0152326. eCollection 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hernandez JD, Nguyen JT, He J, Wang W, Ardman B, Green JM, Fukuda M, Baum LG. Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death. J Immunol. 2006;177(8):5328–36.PubMedCrossRefGoogle Scholar
  22. Hickey TB, Ziltener HJ, Speert DP, Stokes RW. Mycobacterium tuberculosis employs Cpn60.2 as an adhesin that binds CD43 on the macrophage surface. Cell Microbiol. 2010;12(11):1634–47.PubMedCrossRefGoogle Scholar
  23. Humbria A, Diaz-Gonzalez F, Campanero MR, Arroyo AG, Laffon A, Gonzalez-Amaro R, et al. Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from patients with inflammatory joint diseases. Evid soluble form L selectin synovial fluid Arthritis Rheum. 1994;37(3):342–8.Google Scholar
  24. Inui M, Hirota S, Hirano K, Fujii H, Sugahara-Tobinai A, Ishii T, et al. Human CD43+ B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals. Int Immunol. 2015;27(7):345–355. doi:10.1093/intimm/dxv009. Epub 2015 Mar 5.CrossRefPubMedGoogle Scholar
  25. Johnson GG, Mikulowska A, Butcher EC, McEvoy LM, Michie SA. Anti-CD43 monoclonal antibody L11 blocks migration of T cells to inflamed pancreatic islets and prevents development of diabetes in nonobese diabetic mice. J Immunol. 1999;163(10):5678–85.PubMedPubMedCentralGoogle Scholar
  26. Kadaja L, Laos S, Maimets T. Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF. Oncogene. 2004;23(14):2523–30.PubMedCrossRefGoogle Scholar
  27. Kadaja-Saarepuu L, Laos S, Jaager K, Viil J, Balikova A, Looke M, et al. CD43 promotes cell growth and helps to evade FAS-mediated apoptosis in non-hematopoietic cancer cells lacking the tumor suppressors p53 or ARF. Oncogene. 2008;27(12):1705–15 .Epub 2007 Sep 24PubMedCrossRefGoogle Scholar
  28. Khunkaewla P, Schiller HB, Paster W, Leksa V, Cermak L, Andera L, Horejsí V, Stockinger H. LFA-1-mediated leukocyte adhesion regulated by interaction of CD43 with LFA-1 and CD147. Mol Immunol. 2008;45(6):1703–11.PubMedCrossRefGoogle Scholar
  29. Lanteri M, Giordanengo V, Hiraoka N, Fuzibet JG, Auberger P, Fukuda M, et al. Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death. Glycobiology. 2003;13(12):909–18.PubMedCrossRefGoogle Scholar
  30. Laos S, Baeckström D, Hansson GC. Inhibition of NF-kB activation and chemokine expression by the leukocyte glycoprotein CD43 in colon cancer cells. Int J Oncol. 2006;28(3):695–704.PubMedPubMedCentralGoogle Scholar
  31. Leong AS, Cooper K, Leong FJ. Manual for diagnostic antibodies for immunohistology. 2nd ed. London: Greenwich Medical Media Ltd; 2003.Google Scholar
  32. Lopez S, Seveau S, Lesavre P, Robinson MK, Halbwachs-Mecarelli L. CD43 (sialophorin, leukosialin) shedding is an initial event during neutrophil migration, which could be closely related to the spreading of adherent cells. Cell Adhes Commun. 1998;5(2):151–60.PubMedCrossRefGoogle Scholar
  33. Manjunath N, Correa M, Ardman M, Ardman B. Negative regulation of T-cell adhesion and activation by CD43. Nature. 1995;377(6549):535–8.PubMedCrossRefGoogle Scholar
  34. Matsumoto M, Shigeta A, Miyasaka M, Hirata T. CD43 plays both antiadhesive and proadhesive roles in neutrophil rolling in a context-dependent manner. J Immunol. 2008;181(5):3628–35.PubMedCrossRefGoogle Scholar
  35. Miki Y, Itoh T, Hirano K, Eda S, Hayashi A, Yamanaka M, Beppu M. Clearance of oxidatively damaged cells by macrophages: recognition of glycoprotein clusters by macrophage-surface nucleolin as early apoptotic cells. Biol Pharm Bull. 2009;32(4):564–72.PubMedCrossRefGoogle Scholar
  36. Miki Y, Oguri E, Hirano K, Beppu M. Macrophage recognition of cells with elevated calcium is mediated by carbohydrate chains of CD43. Cell Struct Funct. 2013;38(1):43–54. Epub 2013 Feb 9.PubMedCrossRefGoogle Scholar
  37. Misawa Y, Nagaoka H, Kimoto H, Ishii Y, Kitamura K, Tsunetsugu-Yokota Y, Shibuya M, Takemori T. CD43 expression in a B cell lymphoma, WEHI 231, reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion. Eur J Immunol. 1996;26(11):2573–81.PubMedCrossRefGoogle Scholar
  38. Montiel JL, Monsivais-Urenda A, Figueroa-Vega N, Moctezuma JF, Burgos-Vargas R, Gonzalez-Amaro R, Rosenstein Y. Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus erythematosus. Scand J Rheumatol. 2010;39(1):50–7.PubMedCrossRefGoogle Scholar
  39. Nonomura C, Kikuchi J, Kiyokawa N, Ozaki H, Mitsunaga K, Ando H, et al. CD43, but not P-selectin glycoprotein ligand-1, functions as an E-selectin counter-receptor in human pre-B-cell leukemia NALL-1. Cancer Res. 2008;68(3):790–9.PubMedCrossRefGoogle Scholar
  40. Onami TM, Harrington LE, Williams MA, Galvan M, Larsen CP, Pearson TC, et al. Dynamic regulation of T cell immunity by CD43. J Immunol. 2002;168(12):6022–31.PubMedCrossRefGoogle Scholar
  41. Ostberg JR, Barth RK, Frelinger JG. The Roman god Janus: a paradigm for the function of CD43. Immunol Today. 1998;19(12):546–50.PubMedCrossRefGoogle Scholar
  42. Pallant A, Eskenazi A, Mattei MG, Fournier RE, Carlsson SR, Fukuda M, Frelinger JG. Characterization of cDNAs encoding human leukosialin and localization of the leukosialin gene to chromosome 16. Proc Natl Acad Sci USA. 1989;86(4):1328–32.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Pedraza-Alva G, Rosenstein Y. CD43: one molecule, many tales to recount. Signal Transduction. 2007;7:372–85.CrossRefGoogle Scholar
  44. Remold-O’Donnell E, Kenney DM, Parkman R, Cairns L, Savage B, Rosen FS. Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiskott-Aldrich syndrome. J Exp Med. 1984;159(6):1705–23.PubMedCrossRefGoogle Scholar
  45. Ruhl S, Cisar JO, Sandberg AL. Identification of polymorphonuclear leukocyte and HL-60 cell receptors for adhesins of Streptococcus gordonii and Actinomyces naeslundii. Infect Immun. 2000;68(11):6346–54.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Sakkas LI, Scanzello C, Johanson N, Burkholder J, Mitra A, Salgame P, et al. T cells and T-cell cytokine transcripts in the synovial membrane in patients with osteoarthritis. Clin Diagn Lab Immunol. 1998;5(4):430–7.PubMedPubMedCentralGoogle Scholar
  47. Seo W, Ziltener HJ. CD43 processing and nuclear translocation of CD43 cytoplasmic tail are required for cell homeostasis. Blood. 2009;114(17):3567–77.PubMedCrossRefGoogle Scholar
  48. Sperling AI, Green JM, Mosley RL, Smith PL, DiPaolo RJ, Klein JR, Bluestone JA, Thompson CB. CD43 is a murine T cell costimulatory receptor that functions independently of CD28. J Exp Med. 1995;182(1):139–46.PubMedCrossRefGoogle Scholar
  49. Szabady RL, Lokuta MA, Walters KB, Huttenlocher A, Welch RA. Modulation of neutrophil function by a secreted mucinase of Escherichia coli O157:H7. PLoS Pathog. 2009;5(2):e1000320.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Tuccillo FM, de Laurentiis A, Camillo Palmieri C, Fiume G, Bonelli P, Borrelli A, et al. Aberrant glycosylation as biomarker for cancer: Focus on CD43. BioMed Res Int. 2014;2014:742831. doi:10.1155/2014/742831. Epub 2014 Feb 13.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Velázquez F, Grodecki-Pena A, Knapp A, Salvador AM, Nevers T, Croce KJ, et al. CD43 functions as an E-selectin ligand for Th17 cells in vitro and is required for rolling on the vascular endothelium and Th17 cell recruitment during inflammation in vivo. J Immunol. 2016;196(3):1305–16. doi:10.4049/jimmunol.1501171. Epub 2015 Dec 23.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Zemelman BV, Chu SH, Walker WA. Host response to Escherichia coli heat-labile enterotoxin via two microvillus membrane receptors in the rat intestine. Infect Immun. 1989;57(10):2947–52.PubMedPubMedCentralGoogle Scholar
  53. Zhou H, Yan H, Cannon JL, Springer LE, Green JM, Pham CTN. CD43-mediated IFN-g production by CD8+ T cells promotes abdominal aortic aneurysm in mice. J Immunol. 2013;190(10):5078–85. doi:10.4049/jimmunol.1203228. Epub 2013 Apr 12.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Alvaro Torres-Huerta
    • 1
    Email author
  • Estefania Aleman-Navarro
    • 1
  • Maria Elena Bravo-Adame
    • 1
  • Monserrat Alba Sandoval-Hernandez
    • 1
  • Oscar Arturo Migueles-Lozano
    • 1
  • Yvonne Rosenstein
    • 1
  1. 1.Instituto de BiotecnologíaUniversidad Nacional Autónoma de MéxicoCuernavacaMexico