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Gene Review

Itga4  -  integrin alpha 4

Mus musculus

Synonyms: CD49 antigen-like family member D, CD49D, Integrin alpha-4, Integrin alpha-IV, Itga4B, ...
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Disease relevance of Itga4


High impact information on Itga4


Chemical compound and disease context of Itga4

  • Transfectants of the B cell lymphoma 38C13 were generated that differ exclusively in the expression of integrin beta 1 or beta 7 subunits allowing for a functional comparison of lymphocyte Peyer's patch HEV adhesion molecule 1 (LPAM-1) (alpha 4 beta 7) and very late antigen 4 (VLA-4) (alpha 4 beta 1) in an identical cellular environment [8].
  • RESULTS: Early treatment with anti-VLA-4 mAb from days 5-13 showed a significant effect on renal function, with a reduction in albuminuria (p < 0.01) and a higher creatinine clearance (p < 0.05) [9].
  • A nonpeptidyl small molecule antagonist, compound A, to nonactivated very late antigen-4 (VLA4) was examined in lung inflammation induced by a single dose of ovalbumin challenge [10].

Biological context of Itga4


Anatomical context of Itga4


Associations of Itga4 with chemical compounds

  • Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons [20].
  • However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca(2+)-, Mg(2+)-independent, LFA-1/ICAM-1-, CD2/LFA-3, VLA-4/VCAM-1-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment [21].
  • Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1 [22].
  • The VLA-4 (alpha 4 beta 1) integrin is a leukocyte glycoprotein involved in both cell-extracellular matrix and cell-cell interactions [23].
  • Flow cytometric analysis revealed increased expression of CD11b and VLA-4 on leukocytes attached to platelets after allergen exposure, and CD11b expression on leukocytes was suppressed in thrombocytopenic mice but was restored with the transfusion of FSPs, but not FUSPs, a phenomenon concurrent with the formation of platelet-leukocyte complexes [24].

Physical interactions of Itga4


Regulatory relationships of Itga4


Other interactions of Itga4

  • To identify the importance of VLA-4, CD44, ICAM-1 and MAC-1 in the pathogenesis of SFV infection, monoclonal antibodies that block these adhesion molecules were administered in vivo during infection [2].
  • However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1 [31].
  • Infiltrated eosinophils and mononuclear cells in the skin expressed Mac-1 (eosinophils: 38.9 +/- 1.55%, mononuclear cells: 51.2 +/- 2.15%), LFA-1 (eosinophils: 33.3 +/- 0.95%, mononuclear cells: 23.1 +/- 1.07%) and VLA-4 (eosinophils: 14.3 +/- 1.6%, mononuclear cells: 17.2 +/- 1.38%) at 12 h [32].
  • This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM [1].
  • Role of very-late antigen-4 (VLA-4) in myelin basic protein-primed T cell contact-induced expression of proinflammatory cytokines in microglial cells [33].

Analytical, diagnostic and therapeutic context of Itga4


  1. Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells. Franitza, S., Grabovsky, V., Wald, O., Weiss, I., Beider, K., Dagan, M., Darash-Yahana, M., Nagler, A., Brocke, S., Galun, E., Alon, R., Peled, A. Eur. J. Immunol. (2004) [Pubmed]
  2. A role for alpha4-integrin in the pathology following Semliki Forest virus infection. Smith, J.P., Morris-Downes, M., Brennan, F.R., Wallace, G.J., Amor, S. J. Neuroimmunol. (2000) [Pubmed]
  3. Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation. Qian, F., Vaux, D.L., Weissman, I.L. Cell (1994) [Pubmed]
  4. Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells. Matsuura, N., Puzon-McLaughlin, W., Irie, A., Morikawa, Y., Kakudo, K., Takada, Y. Am. J. Pathol. (1996) [Pubmed]
  5. CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Levy, S., Todd, S.C., Maecker, H.T. Annu. Rev. Immunol. (1998) [Pubmed]
  6. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Berlin, C., Berg, E.L., Briskin, M.J., Andrew, D.P., Kilshaw, P.J., Holzmann, B., Weissman, I.L., Hamann, A., Butcher, E.C. Cell (1993) [Pubmed]
  7. Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Rosen, G.D., Sanes, J.R., LaChance, R., Cunningham, J.M., Roman, J., Dean, D.C. Cell (1992) [Pubmed]
  8. Distinct binding specificities of integrins alpha 4 beta 7 (LPAM-1), alpha 4 beta 1 (VLA-4), and alpha IEL beta 7. Strauch, U.G., Lifka, A., Gosslar, U., Kilshaw, P.J., Clements, J., Holzmann, B. Int. Immunol. (1994) [Pubmed]
  9. Blocking VLA-4 prevents progression of experimental crescentic glomerulonephritis. Khan, S.B., Allen, A.R., Bhangal, G., Smith, J., Lobb, R.R., Cook, H.T., Pusey, C.D. Nephron Exp. Nephrol. (2003) [Pubmed]
  10. A small molecule very late antigen-4 antagonist can inhibit ovalbumin-induced lung inflammation. Koo, G.C., Shah, K., Ding, G.J., Xiao, J., Wnek, R., Doherty, G., Tong, X.C., Pepinsky, R.B., Lin, K.C., Hagmann, W.K., Kawka, D., Singer, I.I. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  11. LFA-1 is required for retention of effector CD8 T cells in mouse lungs. Thatte, J., Dabak, V., Williams, M.B., Braciale, T.J., Ley, K. Blood (2003) [Pubmed]
  12. Adhesion molecules in hematopoietic cells. Kinashi, T., Springer, T.A. Blood Cells (1994) [Pubmed]
  13. Changes in cell adhesion molecule expression on T cells associated with systemic virus infection. Andersson, E.C., Christensen, J.P., Marker, O., Thomsen, A.R. J. Immunol. (1994) [Pubmed]
  14. Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4. Selmaj, K., Walczak, A., Mycko, M., Berkowicz, T., Kohno, T., Raine, C.S. Eur. J. Immunol. (1998) [Pubmed]
  15. Essential role of VLA-4/VCAM-1 pathway in the establishment of CD8+ T-cell-mediated Trypanosoma cruzi-elicited meningoencephalitis. Roffê, E., Silva, A.A., Marino, A.P., dos Santos, P.V., Lannes-Vieira, J. J. Neuroimmunol. (2003) [Pubmed]
  16. Structural requirements for mucosal vascular addressin binding to its lymphocyte receptor alpha 4 beta 7. Common themes among integrin-Ig family interactions. Briskin, M.J., Rott, L., Butcher, E.C. J. Immunol. (1996) [Pubmed]
  17. In vitro invasiveness of CTL clones and in vivo dissemination of CTL hybridomas. La Rivière, G., Gebbinck, J.W., Schipper, C.A., Mooi, W.J., Roos, E. J. Leukoc. Biol. (1993) [Pubmed]
  18. Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system. Brown, H.C., Castaño, A., Fearn, S., Townsend, M., Edwards, G., Streuli, C., Perry, V.H. Eur. J. Neurosci. (1997) [Pubmed]
  19. Integrin alpha 4 beta 7 mediates human eosinophil interaction with MAdCAM-1, VCAM-1 and fibronectin. Walsh, G.M., Symon, F.A., Lazarovils, A.L., Wardlaw, A.J. Immunology (1996) [Pubmed]
  20. Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons. Hikita, S.T., Cann, G.M., Wingerd, K.L., Mullick, L.H., Wayne, W.C., Webb, S.W., Clegg, D.O. Mol. Cell. Neurosci. (2003) [Pubmed]
  21. Activation of CD44 induces ICAM-1/LFA-1-independent, Ca2+, Mg(2+)-independent adhesion pathway in lymphocyte-endothelial cell interaction. Toyama-Sorimachi, N., Miyake, K., Miyasaka, M. Eur. J. Immunol. (1993) [Pubmed]
  22. Prostaglandin E1 inhibits TNF alpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells. Weiss, J.M., Pilarski, K.A., Weyl, A., Peschen, M., Schöpf, E., Vestweber, D., Vanscheidt, W., Simon, J.C. Exp. Dermatol. (1995) [Pubmed]
  23. The genomic structure of the murine alpha 4 integrin gene. De Meirsman, C., Jaspers, M., Schollen, E., Cassiman, J.J. DNA Cell Biol. (1996) [Pubmed]
  24. Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Pitchford, S.C., Momi, S., Giannini, S., Casali, L., Spina, D., Page, C.P., Gresele, P. Blood (2005) [Pubmed]
  25. IL-7 activates alpha4beta1 integrin in murine thymocytes. Kitazawa, H., Muegge, K., Badolato, R., Wang, J.M., Fogler, W.E., Ferris, D.K., Lee, C.K., Candéias, S., Smith, M.R., Oppenheim, J.J., Durum, S.K. J. Immunol. (1997) [Pubmed]
  26. Murine vascular cell adhesion molecule-1 (VCAM-1) proteins encoded by alternatively spliced mRNAs are differentially targeted in polarized cells. Pirozzi, G., Terry, R.W., Labow, M.A. Cell Adhes. Commun. (1994) [Pubmed]
  27. Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment. Carrithers, M.D., Visintin, I., Kang, S.J., Janeway, C.A. Brain (2000) [Pubmed]
  28. CD8(+) T cells secreting type 2 lymphokines are defective in protection against viral infection. Wirth, S., van den Broek, M., Frossard, C.P., Hügin, A.W., Leblond, I., Pircher, H., Hauser, C. Cell. Immunol. (2000) [Pubmed]
  29. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Guan, J.L., Hynes, R.O. Cell (1990) [Pubmed]
  30. Differential utilization of VLA-4 (alpha 4 beta 1) and -5 (alpha 5 beta 1) integrins during the development of mouse bone marrow-derived mast cells. Fehlner-Gardiner, C.C., Uniyal, S., von Ballestrem, C.G., Chan, B.M. Differentiation (1996) [Pubmed]
  31. The low molecular weight Dextran 40 inhibits the adhesion of T lymphocytes to endothelial cells. Termeer, C.C., Weiss, J.M., Schöpf, E., Vanscheidt, W., Simon, J.C. Clin. Exp. Immunol. (1998) [Pubmed]
  32. The inhibitory effect of anti-adhesion molecule antibodies on eosinophil infiltration in cutaneous late phase response in Balb/c mice sensitized with ovalbumin (OVA). Hakugawa, J., Bae, S.J., Tanaka, Y., Katayama, I. J. Dermatol. (1997) [Pubmed]
  33. Role of very-late antigen-4 (VLA-4) in myelin basic protein-primed T cell contact-induced expression of proinflammatory cytokines in microglial cells. Dasgupta, S., Jana, M., Liu, X., Pahan, K. J. Biol. Chem. (2003) [Pubmed]
  34. Intracellular single-chain antibody inhibits integrin VLA-4 maturation and function. Yuan, Q., Strauch, K.L., Lobb, R.R., Hemler, M.E. Biochem. J. (1996) [Pubmed]
  35. In vivo microscopy of murine islets of Langerhans: increased adhesion of transferred lymphocytes to islets depends on macrophage-derived cytokines in a model of organ-specific insulitis. Ludwig, R., Kretschmer, M., Caspar, G., Bojunga, J., Oldenburg, A., Schumm-Draeger, P., Stegmüller, M., von Minckwitz, G., Usadel, K.H., Kusterer, K. Immunology (1999) [Pubmed]
  36. Blockade of integrin VLA-4 prevents inflammation and matrix metalloproteinase expression in a murine model of accelerated collagen-induced arthritis. Raychaudhuri, A., Chou, M., Weetall, M., Jeng, A.Y. Inflammation (2003) [Pubmed]
  37. Alpha4beta1 integrin (VLA-4) blockade attenuates both early and late leukocyte recruitment and neointimal growth following carotid injury in apolipoprotein E (-/-) mice. Barringhaus, K.G., Phillips, J.W., Thatte, J.S., Sanders, J.M., Czarnik, A.C., Bennett, D.K., Ley, K.F., Sarembock, I.J. J. Vasc. Res. (2004) [Pubmed]
  38. Association between ICAM-1 expression and metastatic capacity of murine B-cell hybridomas. Hawley, R.G., Wang, M.H., Fong, A.Z., Hawley, T.S. Clin. Exp. Metastasis (1993) [Pubmed]
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