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Gene Review

ICAM3  -  intercellular adhesion molecule 3

Homo sapiens

Synonyms: CD50, CDW50, CDw50, ICAM-3, ICAM-R, ...
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Disease relevance of ICAM3


High impact information on ICAM3

  • Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses [6].
  • Here, we demonstrate that ICAM-3 expressed by resting T cells is important in this first contact with DC [6].
  • ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains [7].
  • Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12) [7].
  • The high level of expression of ICAM-R on resting leukocytes of all lineages and its lack of expression on either resting or cytokine-activated endothelial cells indicates a pattern of expression distinct from ICAM-1 and ICAM-2 [8].

Chemical compound and disease context of ICAM3


Biological context of ICAM3

  • The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin-family type domains [8].
  • Altogether, these data indicate that moesin interacts with ICAM-3 and CD44 adhesion molecules in uropods of polarized T cells; these data also suggest that these interactions participate in the formation of links between membrane receptors and the cytoskeleton, thereby regulating morphological changes during cell locomotion [12].
  • Analysis of a panel of 45 point mutants of domain 1 of ICAM-3 identified five residues that may contact LFA-1 as part of the binding site, Asn23, Ser25, Glu37, Phe54, and Gln75 [13].
  • In addition to an adhesive function, ICAM-3 can act as a signal-transducing molecule on T cells, providing a costimulatory signal for cell proliferation [14].
  • Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation [15].

Anatomical context of ICAM3

  • Expression of VLA4 and ICAM3 on lymphocytes, however, might be a specific event in all three immune reactions [3].
  • Eosinophils in atopic asthma bronchitis in contrast to COPD bronchitis also expressed both VLA4 and ICAM3 [3].
  • A synthetic peptide containing the Ile-Lys-Gly-Asn motif inhibited ICAM-3-dependent adhesion and proliferation of T cells at micromolar concentrations, suggesting that this peptide interferes with immune recognition [16].
  • ICAM-3 expression on endothelium in lymphoid malignancy [5].
  • In the present study, we show immunocytochemically that ICAM-3 is present on T and B cells in the mantle zones and on a subpopulation of follicular center cells in reactive lymph nodes and only occasionally in endothelium [5].

Associations of ICAM3 with chemical compounds

  • Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M(r) 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function [8].
  • Using a panel of human/murine I domain chimeras and point mutants, we observed that the Ile-Lys-Gly-Asn motif, located in the NH2-terminal part of the CD11a I domain, is required for ICAM-3 but not ICAM-1 binding [16].
  • Thus, ICAM-3 was almost exclusively concentrated in the most distal portion of the heading uropod whereas either LFA-1 or the VLA beta 1 integrin were uniformly distributed all over the large contact area [17].
  • Only SB 203580 could reverse the effect on CD11b, CD18, and ICAM-3 expressions [18].
  • In addition, inhibitors of tyrosine kinase activity also abolished ICAM-3 and LFA-1-mediated cell aggregation [19].
  • Patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P=.0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P=.022; OR, 0.30 [95% CI, 0.10-0.89]) on admission [20].

Physical interactions of ICAM3


Co-localisations of ICAM3


Regulatory relationships of ICAM3


Other interactions of ICAM3


Analytical, diagnostic and therapeutic context of ICAM3


  1. DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. Soilleux, E.J., Barten, R., Trowsdale, J. J. Immunol. (2000) [Pubmed]
  2. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J.L., Arenzana-Seisdedos, F., Desprès, P. EMBO Rep. (2003) [Pubmed]
  3. Expression of adhesion molecules in allergic lung diseases. Popper, H.H., Pailer, S., Wurzinger, G., Feldner, H., Hesse, C., Eber, E. Virchows Arch. (2002) [Pubmed]
  4. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. Bashirova, A.A., Geijtenbeek, T.B., van Duijnhoven, G.C., van Vliet, S.J., Eilering, J.B., Martin, M.P., Wu, L., Martin, T.D., Viebig, N., Knolle, P.A., KewalRamani, V.N., van Kooyk, Y., Carrington, M. J. Exp. Med. (2001) [Pubmed]
  5. ICAM-3 expression on endothelium in lymphoid malignancy. Doussis-Anagnostopoulou, I., Kaklamanis, L., Cordell, J., Jones, M., Turley, H., Pulford, K., Simmons, D., Mason, D., Gatter, K. Am. J. Pathol. (1993) [Pubmed]
  6. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Geijtenbeek, T.B., Torensma, R., van Vliet, S.J., van Duijnhoven, G.C., Adema, G.J., van Kooyk, Y., Figdor, C.G. Cell (2000) [Pubmed]
  7. Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Fawcett, J., Holness, C.L., Needham, L.A., Turley, H., Gatter, K.C., Mason, D.Y., Simmons, D.L. Nature (1992) [Pubmed]
  8. Cloning and characterization of a new intercellular adhesion molecule ICAM-R. Vazeux, R., Hoffman, P.A., Tomita, J.K., Dickinson, E.S., Jasman, R.L., St John, T., Gallatin, W.M. Nature (1992) [Pubmed]
  9. DC-SIGN binds to HIV-1 glycoprotein 120 in a distinct but overlapping fashion compared with ICAM-2 and ICAM-3. Su, S.V., Hong, P., Baik, S., Negrete, O.A., Gurney, K.B., Lee, B. J. Biol. Chem. (2004) [Pubmed]
  10. Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients. Nair, M.P., Mahajan, S.D., Schwartz, S.A., Reynolds, J., Whitney, R., Bernstein, Z., Chawda, R.P., Sykes, D., Hewitt, R., Hsiao, C.B. J. Immunol. (2005) [Pubmed]
  11. Soluble and cell surface ICAM-3 in blood and cerebrospinal fluid of patients with multiple sclerosis: influence of methylprednisolone treatment and relevance as markers for disease activity. Kraus, J., Oschmann, P., Engelhardt, B., Bauer, R., Schiel, C., Kern, A., Stolz, E., Traupe, A., Dorndorf, W. Acta neurologica Scandinavica. (2000) [Pubmed]
  12. Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization. Serrador, J.M., Alonso-Lebrero, J.L., del Pozo, M.A., Furthmayr, H., Schwartz-Albiez, R., Calvo, J., Lozano, F., Sánchez-Madrid, F. J. Cell Biol. (1997) [Pubmed]
  13. Localization of the binding site on intercellular adhesion molecule-3 (ICAM-3) for lymphocyte function-associated antigen 1 (LFA-1). Klickstein, L.B., York, M.R., Fougerolles, A.R., Springer, T.A. J. Biol. Chem. (1996) [Pubmed]
  14. The leukocyte function-associated antigen-1 (LFA-1)-binding site on ICAM-3 comprises residues on both faces of the first immunoglobulin domain. Bell, E.D., May, A.P., Simmons, D.L. J. Immunol. (1998) [Pubmed]
  15. Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium. Comparison with other adhesion molecules. el-Gabalawy, H., Gallatin, M., Vazeux, R., Peterman, G., Wilkins, J. Arthritis Rheum. (1994) [Pubmed]
  16. Critical amino acids in the lymphocyte function-associated antigen-1 I domain mediate intercellular adhesion molecule 3 binding and immune function. van Kooyk, Y., Binnerts, M.E., Edwards, C.P., Champe, M., Berman, P.W., Figdor, C.G., Bodary, S.C. J. Exp. Med. (1996) [Pubmed]
  17. ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands. Campanero, M.R., Sánchez-Mateos, P., del Pozo, M.A., Sánchez-Madrid, F. J. Cell Biol. (1994) [Pubmed]
  18. Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor-induced adhesion molecule expression on eosinophils by p38 mitogen-activated protein kinase and nuclear factor-[kappa] B. Wong, C.K., Ip, W.K., Lam, C.W. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  19. Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase. Arroyo, A.G., Campanero, M.R., Sánchez-Mateos, P., Zapata, J.M., Ursa, M.A., del Pozo, M.A., Sánchez-Madrid, F. J. Cell Biol. (1994) [Pubmed]
  20. Association of ICAM3 genetic variant with severe acute respiratory syndrome. Chan, K.Y., Ching, J.C., Xu, M.S., Cheung, A.N., Yip, S.P., Yam, L.Y., Lai, S.T., Chu, C.M., Wong, A.T., Song, Y.Q., Huang, F.P., Liu, W., Chung, P.H., Leung, G.M., Chow, E.Y., Chan, E.Y., Chan, J.C., Ngan, H.Y., Tam, P., Chan, L.C., Sham, P., Chan, V.S., Peiris, M., Lin, S.C., Khoo, U.S. J. Infect. Dis. (2007) [Pubmed]
  21. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe? Soilleux, E.J. Clin. Sci. (2003) [Pubmed]
  22. An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alphaLbeta2. Song, G., Yang, Y., Liu, J.H., Casasnovas, J.M., Shimaoka, M., Springer, T.A., Wang, J.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. Internalizing antibodies to the C-type lectins, L-SIGN and DC-SIGN, inhibit viral glycoprotein binding and deliver antigen to human dendritic cells for the induction of T cell responses. Dakappagari, N., Maruyama, T., Renshaw, M., Tacken, P., Figdor, C., Torensma, R., Wild, M.A., Wu, D., Bowdish, K., Kretz-Rommel, A. J. Immunol. (2006) [Pubmed]
  24. ICAM-3-induced cancer cell proliferation through the PI3K/Akt pathway. Kim, Y.G., Kim, M.J., Lim, J.S., Lee, M.S., Kim, J.S., Yoo, Y.D. Cancer Lett. (2006) [Pubmed]
  25. Polarization and interaction of adhesion molecules P-selectin glycoprotein ligand 1 and intercellular adhesion molecule 3 with moesin and ezrin in myeloid cells. Alonso-Lebrero, J.L., Serrador, J.M., Domínguez-Jiménez, C., Barreiro, O., Luque, A., del Pozo, M.A., Snapp, K., Kansas, G., Schwartz-Albiez, R., Furthmayr, H., Lozano, F., Sánchez-Madrid, F. Blood (2000) [Pubmed]
  26. Engagement of the CD45 molecule induces homotypic adhesion of human thymocytes through a LFA-1/ICAM-3-dependent pathway. Bernard, G., Zoccola, D., Ticchioni, M., Breittmayer, J.P., Aussel, C., Bernard, A. J. Immunol. (1994) [Pubmed]
  27. Functional intercellular adhesion molecule-3 is expressed by freshly isolated epidermal Langerhans cells and is not regulated during culture. Zambruno, G., Cossarizza, A., Zacchi, V., Ottani, D., Luppi, A.M., Giannetti, A., Girolomoni, G. J. Invest. Dermatol. (1995) [Pubmed]
  28. The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells. Griffiths, C.E., Railan, D., Gallatin, W.M., Cooper, K.D. Br. J. Dermatol. (1995) [Pubmed]
  29. A novel leukointegrin, alpha d beta 2, binds preferentially to ICAM-3. Van der Vieren, M., Le Trong, H., Wood, C.L., Moore, P.F., St John, T., Staunton, D.E., Gallatin, W.M. Immunity (1995) [Pubmed]
  30. Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor for Leishmania amastigotes. Colmenares, M., Puig-Kröger, A., Pello, O.M., Corbí, A.L., Rivas, L. J. Biol. Chem. (2002) [Pubmed]
  31. Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of association with cICAM-1. Martin, S., Rieckmann, P., Melchers, I., Wagner, R., Bertrams, J., Voskuyl, A.E., Roep, B.O., Zielasek, J., Heidenthal, E., Weichselbraun, I. J. Immunol. (1995) [Pubmed]
  32. Analysis of the binding site on intercellular adhesion molecule 3 for the leukocyte integrin lymphocyte function-associated antigen 1. Holness, C.L., Bates, P.A., Little, A.J., Buckley, C.D., McDowall, A., Bossy, D., Hogg, N., Simmons, D.L. J. Biol. Chem. (1995) [Pubmed]
  33. Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood eosinophils and neutrophils. Kessel, J.M., Sedgwick, J.B., Busse, W.W. J. Allergy Clin. Immunol. (2006) [Pubmed]
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