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Gene Review

ICAM2  -  intercellular adhesion molecule 2

Homo sapiens

Synonyms: CD102, ICAM-2, Intercellular adhesion molecule 2
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Disease relevance of ICAM2


Psychiatry related information on ICAM2

  • In this study, 13 clinically and pathologically diagnosed cases of Alzheimer's disease were analyzed for the presence of intercellular adhesion molecule 1 (ICAM-1), ICAM-2, lymphocyte function associated antigen-1 (LFA-1), HLA-DR, LN-1, and LN-2 [6].

High impact information on ICAM2


Chemical compound and disease context of ICAM2


Biological context of ICAM2

  • Hybridization of an ICAM2 cDNA clone to Southern blots from this panel indicates that the human ICAM2 gene maps to chromosome 17 region q23-25 [12].
  • Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1) [13].
  • We show that mutation of the serine phosphorylation site leads to inability of Mac-1 to become activated to bind the cellular ligands ICAM-1 and ICAM-2 [14].
  • The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a framework for understanding the role of glycosylation in the structure and function of intercellular adhesion molecules (ICAMs) [15].
  • Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels [16].

Anatomical context of ICAM2

  • We have used a panel of somatic cell hybrids and chromosome-mediated gene transfectants to establish the chromosomal location of the gene for ICAM2 [12].
  • In adhesion assays, resting and stimulated platelets were capable of binding through ICAM-2 to purified leukocyte function-associated antigen-1 [1].
  • Staining of bone marrow aspirates with anti-ICAM-2 mAb demonstrates strong reactivity to megakaryocytes [1].
  • A variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM-1, ICAM-2 staining was demonstrable in the vascular endothelium of both normal and inflamed tissues, the latter demonstrating a significantly higher proportion of positive vessels [16].
  • Solid-phase recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co-stimulate CD4+ T lymphocyte proliferation in conjunction with suboptimal solid-phase CD3 mAb 64 [17].

Associations of ICAM2 with chemical compounds


Physical interactions of ICAM2


Regulatory relationships of ICAM2

  • After 48-72-h culture in the presence of granulocyte/macrophage colony-stimulating factor, LC did not stain for ICAM-2 but expressed ICAM-3 at the same level as fresh cells [26].
  • The addition of mAb directed at the CD11a or CD18 molecules almost completely inhibited the responses to ICAM-2 Rg [23].
  • The activity of an ICAM-2 promoter reporter plasmid transfected into HUVECs was down-regulated by TNF-alpha and IL-1beta to similar values [27].
  • METHODS: Transgenic mice expressing pig CD59 or human CD59 under the control of the human ICAM-2 promoter, which restricts expression in tissues to vascular endothelium, were used [28].

Other interactions of ICAM2

  • VLA-4 additionally binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion [29].
  • Based on the crystal structure of ICAM-2, we propose a model for the Ig-like domains D1 and D2 of ICAM-4 [30].
  • ERM proteins function as membrane organizers and may act as linkers between plasma membrane molecules, such as CD44 and ICAM-2, and the cytoskeleton [31].
  • However, ICAM-2, B7-1 and B7-2 were not detected, and cytokines failed to induce these molecules [32].
  • This inward migration is associated with progressive vascularisation, ICAM-2 expression and co-localises with GFAP and vimentin positive radial glia [33].

Analytical, diagnostic and therapeutic context of ICAM2


  1. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. Diacovo, T.G., deFougerolles, A.R., Bainton, D.F., Springer, T.A. J. Clin. Invest. (1994) [Pubmed]
  2. Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte function-associated molecule 1 in human immunodeficiency virus-mediated syncytia formation. Butini, L., De Fougerolles, A.R., Vaccarezza, M., Graziosi, C., Cohen, D.I., Montroni, M., Springer, T.A., Pantaleo, G., Fauci, A.S. Eur. J. Immunol. (1994) [Pubmed]
  3. Beta2 integrin/ICAM expression in Crohn's disease. Bernstein, C.N., Sargent, M., Gallatin, W.M. Clin. Immunol. Immunopathol. (1998) [Pubmed]
  4. 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]
  5. EBV peptide epitope sensitization restores human cytotoxic T cell recognition of Burkitt's lymphoma cells. Evidence for a critical role for ICAM-2. Khanna, R., Burrows, S.R., Suhrbier, A., Jacob, C.A., Griffin, H., Misko, I.S., Sculley, T.B., Rowe, M., Rickinson, A.B., Moss, D.J. J. Immunol. (1993) [Pubmed]
  6. Expression of intercellular adhesion molecule 1 (ICAM-1) in Alzheimer's disease. Frohman, E.M., Frohman, T.C., Gupta, S., de Fougerolles, A., van den Noort, S. J. Neurol. Sci. (1991) [Pubmed]
  7. Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface. Casasnovas, J.M., Springer, T.A., Liu, J.H., Harrison, S.C., Wang, J.H. Nature (1997) [Pubmed]
  8. Activation of the PKB/AKT pathway by ICAM-2. Perez, O.D., Kinoshita, S., Hitoshi, Y., Payan, D.G., Kitamura, T., Nolan, G.P., Lorens, J.B. Immunity (2002) [Pubmed]
  9. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Geijtenbeek, T.B., Krooshoop, D.J., Bleijs, D.A., van Vliet, S.J., van Duijnhoven, G.C., Grabovsky, V., Alon, R., Figdor, C.G., van Kooyk, Y. Nat. Immunol. (2000) [Pubmed]
  10. Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells. Jonjić, N., Peri, G., Bernasconi, S., Sciacca, F.L., Colotta, F., Pelicci, P., Lanfrancone, L., Mantovani, A. J. Exp. Med. (1992) [Pubmed]
  11. A monoclonal antibody to the human leukocyte adhesion molecule intercellular adhesion molecule-2. Cellular distribution and molecular characterization of the antigen. Nortamo, P., Salcedo, R., Timonen, T., Patarroyo, M., Gahmberg, C.G. J. Immunol. (1991) [Pubmed]
  12. The human ICAM2 gene maps to 17q23-25. Sansom, D., Borrow, J., Solomon, E., Trowsdale, J. Genomics (1991) [Pubmed]
  13. Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily. Casasnovas, J.M., Pieroni, C., Springer, T.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  14. {alpha}-Chain phosphorylation of the human leukocyte CD11b/CD18 (Mac-1) integrin is pivotal for integrin activation to bind ICAMs and leukocyte extravasation. Fagerholm, S.C., Varis, M., Stefanidakis, M., Hilden, T.J., Gahmberg, C.G. Blood (2006) [Pubmed]
  15. Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs). Jiménez, D., Roda-Navarro, P., Springer, T.A., Casasnovas, J.M. J. Biol. Chem. (2005) [Pubmed]
  16. 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]
  17. Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells. Starling, G.C., McLellan, A.D., Egner, W., Sorg, R.V., Fawcett, J., Simmons, D.L., Hart, D.N. Eur. J. Immunol. (1995) [Pubmed]
  18. Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2. Larson, R.S., Brown, D.C., Sklar, L.A. Blood (1997) [Pubmed]
  19. Distribution of immunoglobulin superfamily members ICAM-1, -2, -3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions. Bö, L., Peterson, J.W., Mørk, S., Hoffman, P.A., Gallatin, W.M., Ransohoff, R.M., Trapp, B.D. J. Neuropathol. Exp. Neurol. (1996) [Pubmed]
  20. Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils. González-Alvaro, I., Carmona, L., Díaz-González, F., González-Amaro, R., Mollinedo, F., Sánchez-Madrid, F., Laffón, A., García-Vicuña, R. J. Rheumatol. (1996) [Pubmed]
  21. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. Weber, C., Springer, T.A. J. Clin. Invest. (1997) [Pubmed]
  22. Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain. Xie, J., Li, R., Kotovuori, P., Vermot-Desroches, C., Wijdenes, J., Arnaout, M.A., Nortamo, P., Gahmberg, C.G. J. Immunol. (1995) [Pubmed]
  23. Intercellular adhesion molecule-2, a second counter-receptor for CD11a/CD18 (leukocyte function-associated antigen-1), provides a costimulatory signal for T-cell receptor-initiated activation of human T cells. Damle, N.K., Klussman, K., Aruffo, A. J. Immunol. (1992) [Pubmed]
  24. A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18. Li, R., Xie, J., Kantor, C., Koistinen, V., Altieri, D.C., Nortamo, P., Gahmberg, C.G. J. Cell Biol. (1995) [Pubmed]
  25. Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of the adhesion protein ICAM-2. Hamada, K., Shimizu, T., Matsui, T., Tsukita, S., Tsukita, S., Hakoshima, T. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
  26. 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]
  27. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium. McLaughlin, F., Hayes, B.P., Horgan, C.M., Beesley, J.E., Campbell, C.J., Randi, A.M. Cell Adhes. Commun. (1998) [Pubmed]
  28. The pig analogue of CD59 protects transgenic mouse hearts from injury by human complement. Fisicaro, N., Aminian, A., Hinchliffe, S.J., Morgan, B.P., Pearse, M.J., D'Apice, A.J., Cowan, P.J. Transplantation (2000) [Pubmed]
  29. Adhesion receptor profile of thymic B-cell lymphoma. Eichelmann, A., Koretz, K., Mechtersheimer, G., Möller, P. Am. J. Pathol. (1992) [Pubmed]
  30. Binding sites of leukocyte beta 2 integrins (LFA-1, Mac-1) on the human ICAM-4/LW blood group protein. Hermand, P., Huet, M., Callebaut, I., Gane, P., Ihanus, E., Gahmberg, C.G., Cartron, J.P., Bailly, P. J. Biol. Chem. (2000) [Pubmed]
  31. Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. Sainio, M., Zhao, F., Heiska, L., Turunen, O., den Bakker, M., Zwarthoff, E., Lutchman, M., Rouleau, G.A., Jääskeläinen, J., Vaheri, A., Carpén, O. J. Cell. Sci. (1997) [Pubmed]
  32. Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells. Matsuoka, N., Eguchi, K., Kawakami, A., Tsuboi, M., Kawabe, Y., Aoyagi, T., Nagataki, S. Clin. Exp. Immunol. (1996) [Pubmed]
  33. Microglia in the human fetal spinal cord--patterns of distribution, morphology and phenotype. Rezaie, P., Patel, K., Male, D.K. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  34. Intercellular adhesion molecule-2 (ICAM-2) expression on human dendritic cells. Hart, D.N., Prickett, T.C. Cell. Immunol. (1993) [Pubmed]
  35. The human leukocyte-adhesion ligand, intercellular-adhesion molecule 2. Expression and characterization of the protein. Gahmberg, C.G., Nortamo, P., Zimmermann, D., Ruoslahti, E. Eur. J. Biochem. (1991) [Pubmed]
  36. Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. Yonemura, S., Hirao, M., Doi, Y., Takahashi, N., Kondo, T., Tsukita, S., Tsukita, S. J. Cell Biol. (1998) [Pubmed]
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