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Gene Review

ITGAX  -  integrin, alpha X (complement component 3...

Homo sapiens

Synonyms: CD11 antigen-like family member C, CD11C, CD11c, Integrin alpha-X, Leu M5, ...
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Disease relevance of ITGAX


Psychiatry related information on ITGAX


High impact information on ITGAX

  • We have now identified a subset of CD4+ CD11c+ CD3- dendritic cells in the germinal centres [6].
  • The alpha d subunit is more closely related to CD11b and CD11c than to CD11a [7].
  • These results demonstrate that CD11b and CD11c are receptors for CD23 and that this novel ligand pairing regulates important activities of monocytes [8].
  • Analysis of CD11c-enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual "balloon" shape, varies along the length of the small bowel [9].
  • The beta2 family of integrins, CD11a, CD11b, CD11c, and alphad, are expressed on most leukocytes [10].

Chemical compound and disease context of ITGAX


Biological context of ITGAX


Anatomical context of ITGAX

  • Unlike other mast cells, UMC expressed CD11c/CD18 (p150,95) and CD32 (Fc gamma RII) [17].
  • The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain [18].
  • On the other hand, antibodies against CD11b, CD11c, and LB-2 showed only marginal reactivity with highly purified LGL-free T cells [19].
  • Recently, we reported that in U937 cells, expression of the CD11c gene is controlled by an unidentified transcription factor that binds ssDNA [1].
  • During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter [1].

Associations of ITGAX with chemical compounds

  • However, the activation of neutrophils depends on the interaction of CD11c/CD18 with the A alpha-chain of platelet-expressed fibrinogen and the contractile system of neutrophils [20].
  • In order to investigate whether binding of fibrinogen to these integrins is involved, monoclonal antibodies (MoAbs) and Gly-Pro-Arg-Pro (GPRP) peptide that inhibits fibrinogen binding to CD11c/CD18 were checked for their effects on the interaction of activated platelets and neutrophils [20].
  • Genistein, herbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N'-tetraacetic acid blocked the immediate expression of CD64 in a dose-dependent manner, suggesting that the signal is mediated through calcium mobilization and protein tyrosine kinase(s) [21].
  • FACS analysis showed that 1,25-DHCC increased the number of cells expressing CD11b in both DH39 and controls, and the number of cells expressing CD11c in DH39 [22].
  • Although AP-1 mediates the responsiveness to several other differentiating agents including GM-CSF, additional elements are required for induction of the CD11c promoter activity upon Sodium Butyrate-triggered differentiation [23].

Physical interactions of ITGAX

  • In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha [1].
  • We also identified 2 peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18 [24].
  • A soluble fusion protein containing the extracellular domain of ICAM-1 abolished C-GRWSGWPADL-C phage binding to CD11c/CD18 [25].

Regulatory relationships of ITGAX

  • During PMA-induced differentiation, the ability of Puralpha to activate the CD11c promoter in U937 cells increases, as does that of Sp1 [1].
  • CD64 expression is induced in a slow kinetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents [21].
  • Functional inhibition of AP-1 expressed by hairy cells reduced CD11c promoter activity by 80% [4].
  • Like all other WSP tested, they induced an upregulation of CD11b but had no influence on CD11c and, most strikingly, CD62L expression [26].
  • Moreover, synthetic monomeric circular peptide C-GRWSGWPADL-C bound specifically to CD11c/CD18 and inhibited ICAM-1 binding [25].

Other interactions of ITGAX

  • The interaction was specifically inhibited by anti-CD11b or anti-CD11c, respectively, and by anti-CD23 MAbs [8].
  • As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05) [27].
  • CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells [28].
  • MoAbs against CD11c or CD49d had little or no effect [29].
  • The expression of CD11c, CD83, and CCR7 in PA-treated NB4 cells was further increased by tumor necrosis factor (TNF)-alpha treatment [30].

Analytical, diagnostic and therapeutic context of ITGAX


  1. During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter. Shelley, C.S., Teodoridis, J.M., Park, H., Farokhzad, O.C., Böttinger, E.P., Arnaout, M.A. J. Immunol. (2002) [Pubmed]
  2. Beta2 integrin/ICAM expression in Crohn's disease. Bernstein, C.N., Sargent, M., Gallatin, W.M. Clin. Immunol. Immunopathol. (1998) [Pubmed]
  3. Deep venous thrombosis: behaviour of the polymorphonuclear leukocyte integrin pattern at baseline and after in vitro activation. Caimi, G., Tozzi Ciancarelli, M.G., Ferrara, F., Montana, M., Calandrino, V., Canino, B., Lo Presti, R. Clin. Hemorheol. Microcirc. (2005) [Pubmed]
  4. CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD. Nicolaou, F., Teodoridis, J.M., Park, H., Georgakis, A., Farokhzad, O.C., Böttinger, E.P., Da Silva, N., Rousselot, P., Chomienne, C., Ferenczi, K., Arnaout, M.A., Shelley, C.S. Blood (2003) [Pubmed]
  5. Microglia in cerebellar plaques in Alzheimer's disease. Mattiace, L.A., Davies, P., Yen, S.H., Dickson, D.W. Acta Neuropathol. (1990) [Pubmed]
  6. Dendritic cells capable of stimulating T cells in germinal centres. Grouard, G., Durand, I., Filgueira, L., Banchereau, J., Liu, Y.J. Nature (1996) [Pubmed]
  7. 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]
  8. CD23 regulates monocyte activation through a novel interaction with the adhesion molecules CD11b-CD18 and CD11c-CD18. Lecoanet-Henchoz, S., Gauchat, J.F., Aubry, J.P., Graber, P., Life, P., Paul-Eugene, N., Ferrua, B., Corbi, A.L., Dugas, B., Plater-Zyberk, C. Immunity (1995) [Pubmed]
  9. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. Chieppa, M., Rescigno, M., Huang, A.Y., Germain, R.N. J. Exp. Med. (2006) [Pubmed]
  10. alphadbeta2 integrin is expressed on human eosinophils and functions as an alternative ligand for vascular cell adhesion molecule 1 (VCAM-1). Grayson, M.H., Van der Vieren, M., Sterbinsky, S.A., Michael Gallatin, W., Hoffman, P.A., Staunton, D.E., Bochner, B.S. J. Exp. Med. (1998) [Pubmed]
  11. Effects of short-term nitrogen monoxide inhalation on leukocyte adhesion molecules, generation of reactive oxygen species, and cytokine release in human blood. Opdahl, H., Haugen, T., Hagberg, I.A., Aspelin, T., Lyberg, T. Nitric Oxide (2000) [Pubmed]
  12. Effects of 1,25-dihydroxy vitamin D3 on all-trans retinoic acid sensitive and resistant acute promyelocytic leukemia cells. Giannì, M., Terao, M., Gambacorti-Passerini, C., Rambaldi, A., Garattini, E. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  13. Similarities between the sensitivity to 2-chlorodeoxyadenosine of lymphocytes from CLL patients and bryostatin 1-treated WSU-CLL cells: an infrared spectroscopic study. Liu, K.Z., Schultz, C.P., Mohammad, R.M., Al-Katib, A.M., Johnston, J.B., Mantsch, H.H. Cancer Lett. (1998) [Pubmed]
  14. Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Prieto, J., Eklund, A., Patarroyo, M. Cell. Immunol. (1994) [Pubmed]
  15. LPS-induced stimulation of phagocytosis in the sipunculan worm Themiste petricola: possible involvement of human CD14, CD11B and CD11C cross-reactive molecules. Blanco, G.A., Escalada, A.M., Alvarez, E., Hajos, S. Dev. Comp. Immunol. (1997) [Pubmed]
  16. The leukocyte integrins are regulated by transcriptional and post-transcriptional mechanisms in a leukemic cell that overexpresses protein kinase C-zeta. Noti, J.D., Reinemann, B.C., Johnson, A.K. Int. J. Oncol. (2001) [Pubmed]
  17. Immunophenotyping and functional analysis of purified human uterine mast cells. Guo, C.B., Kagey-Sobotka, A., Lichtenstein, L.M., Bochner, B.S. Blood (1992) [Pubmed]
  18. The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain. Bilsland, C.A., Diamond, M.S., Springer, T.A. J. Immunol. (1994) [Pubmed]
  19. CD11a-c/CD18 and GP84 (LB-2) adhesion molecules on human large granular lymphocytes and their participation in natural killing. Timonen, T., Patarroyo, M., Gahmberg, C.G. J. Immunol. (1988) [Pubmed]
  20. Platelet-induced neutrophil activation: platelet-expressed fibrinogen induces the oxidative burst in neutrophils by an interaction with CD11C/CD18. Ruf, A., Patscheke, H. Br. J. Haematol. (1995) [Pubmed]
  21. Rapid and prominent up-regulation of high-affinity receptor for immunoglobulin G (Fc gamma RI) by cross-linking of beta 2 integrins on polymorphonuclear leukocytes. Takano, K., Kaganoi, J., Yamamoto, K., Takahashi, A., Kido, T., Sasada, M. Int. J. Hematol. (2000) [Pubmed]
  22. Transfection of vitamin D receptor cDNA into the monoblastoid cell line U937. The role of vitamin D3 in homotypic macrophage adhesion. Hewison, M., Dabrowski, M., Faulkner, L., Hughson, E., Vadher, S., Rut, A., Brickell, P.M., O'Riordan, J.L., Katz, D.R. J. Immunol. (1994) [Pubmed]
  23. CD11c integrin gene promoter activity during myeloid differentiation. Córbi, A.L., Lopéz-Rodríguez, C. Leuk. Lymphoma (1997) [Pubmed]
  24. Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4. Ihanus, E., Uotila, L.M., Toivanen, A., Varis, M., Gahmberg, C.G. Blood (2007) [Pubmed]
  25. Interaction of ICAM-1 with beta2-integrin CD11c/CD18: Characterization of a peptide ligand that mimics a putative binding site on domain D4 of ICAM-1. Frick, C., Odermatt, A., Zen, K., Mandell, K.J., Edens, H., Portmann, R., Mazzucchelli, L., Jaye, D.L., Parkos, C.A. Eur. J. Immunol. (2005) [Pubmed]
  26. Expression of adhesion molecules on human granulocytes after stimulation with Helicobacter pylori membrane proteins: comparison with membrane proteins from other bacteria. Enders, G., Brooks, W., von Jan, N., Lehn, N., Bayerdörffer, E., Hatz, R. Infect. Immun. (1995) [Pubmed]
  27. Expression of endothelial cell-associated molecules in AML cells. Watarai, M., Miwa, H., Shikami, M., Sugamura, K., Wakabayashi, M., Satoh, A., Tsuboi, K., Imamura, A., Mihara, H., Katoh, Y., Kita, K., Nitta, M. Leukemia (2002) [Pubmed]
  28. Comparative studies of the colonic in situ expression of intercellular adhesion molecules (ICAM-1, -2, and -3), beta2 integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in ulcerative colitis and Crohn's disease. Vainer, B., Nielsen, O.H., Horn, T. Am. J. Surg. Pathol. (2000) [Pubmed]
  29. Surface molecules involved in the adherence of recombinant interferon-gamma (rIFN-gamma)-stimulated human monocytes to vascular endothelial cells. Wang, J., Beekhuizen, H., van Furth, R. Clin. Exp. Immunol. (1994) [Pubmed]
  30. Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell-like. Jin, J.O., Park, H.Y., Kim, J.W., Park, J.I., Hong, Y.S., Min, d.o. .S., Kwak, J.Y. J. Cell. Biochem. (2007) [Pubmed]
  31. Intracellular localization of a leukocyte adhesion glycoprotein family in the tertiary granules of human neutrophils. Lacal, P., Pulido, R., Sánchez-Madrid, F., Cabañas, C., Mollinedo, F. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  32. Human leukaemic (HMC-1) and normal skin mast cells express beta 2-integrins: characterization of beta 2-integrins and ICAM-1 on HMC-1 cells. Weber, S., Babina, M., Feller, G., Henz, B.M. Scand. J. Immunol. (1997) [Pubmed]
  33. Myeloid blood CD11c(+) dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes. Osugi, Y., Vuckovic, S., Hart, D.N. Blood (2002) [Pubmed]
  34. Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty. Inoue, T., Sakai, Y., Morooka, S., Hayashi, T., Takayanagi, K., Takabatake, Y. J. Am. Coll. Cardiol. (1996) [Pubmed]
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