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Gene Review

Itgal  -  integrin alpha L

Mus musculus

Synonyms: (p180), CD11 antigen-like family member A, Cd11a, Integrin alpha-L, LFA-1, ...
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Disease relevance of Itgal


Psychiatry related information on Itgal


High impact information on Itgal


Chemical compound and disease context of Itgal


Biological context of Itgal

  • Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1 [15].
  • Ly-15.2 and LFA-1 show identical tissue distributions, being present on all thymocytes, lymphocytes, and neutrophils, and flow cytofluorometric analysis indicated identical cell surface expression of these molecules [16].
  • These results indicate that LFA-1/ICAM-1 interactions facilitate murine thymic development and suggest that cell adhesion molecules mediate important events in T cell differentiation [17].
  • These results suggest that the CD54/CD11a signal transduction pathway is a critical determinant of MAIDS development, and the lack of an immune response against viral Ag is enough to suppress BM5def replication and to prevent MAIDS [3].
  • These results suggest that the presence of high levels of LFA-1 on T cells is absolutely necessary for their epidermotropic migration, but its up-regulation is neither necessary nor sufficient to trigger the epidermotropic migration [18].

Anatomical context of Itgal


Associations of Itgal with chemical compounds

  • Low levels of alpha4beta1 integrin can be detected on neutrophils from LFA-1(+/+) and (-/-) mice [20].
  • Residence time of adoptively transferred Indium 111 (111In)-labeled D4 cells in lungs of normal and HA-Tg mice as analyzed by dual modality imaging revealed a significantly shorter transit time of 4 hours for the D4 cells upon in vivo blockade of LFA-1 [1].
  • The presence of manganese dramatically enhanced the binding to ICAM-1 of LFA-1 lacking the alpha cytoplasmic domain or both cytoplasmic domains, whereas it had relatively little effect on wild-type LFA-1 or the mutant lacking the beta cytoplasmic domain [21].
  • However, LFA703 did not decrease the expression of LFA-1 on circulating leukocytes [22].
  • Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1 [23].

Physical interactions of Itgal

  • We have investigated the role of the cytoplasmic domains of LFA-1 in binding to ICAM-1 and in postadhesion events [21].
  • LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids [24].
  • LFA-1 binding to ICAM-I provides a costimulatory signal for CD8(+) T cell activation that results in increased IL-2 mRNA levels and protein production to support proliferation [25].
  • These experiments provide direct physical evidence that ligation of the CD3 complex specifically increases the proximity of LFA-1 and microfilaments, which may be relevant to T cell mediated adherence reactions [26].
  • Major histocompatibility complex-restricted antigen receptor on T cells. VIII. Role of the LFA-1 molecule [27].

Co-localisations of Itgal

  • ADAP also colocalized with LFA-1 at the immunological synapse [28].

Regulatory relationships of Itgal

  • Control of leukocyte rolling velocity in TNF-alpha-induced inflammation by LFA-1 and Mac-1 [29].
  • Blocking studies revealed that anti-CD3 induced T cell proliferation and T cell-LC cluster formation was inhibited by both anti-LFA-1 and anti-ICAM-1 mAb suggesting that ICAM-1 expressed on LC must bind to LFA-1 on T cells to facilitate proliferative responses of T cells to anti-CD3 mAb [30].
  • We conclude that LFA-1 participates in LPS-induced lethal shock/liver injury by regulating IL-10 secretion from macrophages and that IL-10 plays a decisive role in resistance to shock/liver injury [31].
  • On the other hand, SP slightly induced LFA-1 mRNA translation and activation signals for integrins [32].
  • However, anti-ICAM-1 mAb and anti-LFA-1 mAb did not alter either 1,25D- or PTH-stimulated receptor activator of NF-kappaB ligand (RANKL) mRNA transcription in bone marrow cultures [33].

Other interactions of Itgal

  • These results suggest that an adhesion cascade, which includes L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT [34].
  • Both alpha4beta1, interacting with ligand VCAM-1, and also LFA-1 participate in substantial lymphocyte recirculation through bone marrow [35].
  • The LFA-1 and Mac-1 beta chains are highly homologous or identical, whereas the alpha chains are highly different by tyrosyl tryptic peptide mapping (Kürzinger, K., Ho, M. K., and Springer, T. A. (1982) Nature (Lond.) 296, 668-670) [2].
  • Serum levels of IL-10 in LFA-1(+/-) mice were only marginally affected by macrophage depletion [31].
  • Thus, we propose that (1) peptide-MHC density and (2) accessory molecules such as LFA-1 determine T helper polarization by regulation of CD40L [36].

Analytical, diagnostic and therapeutic context of Itgal


  1. 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]
  2. Purification and structural characterization of LFA-1, a lymphocyte function-associated antigen, and Mac-1, a related macrophage differentiation antigen associated with the type three complement receptor. Kürzinger, K., Springer, T.A. J. Biol. Chem. (1982) [Pubmed]
  3. Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a. Makino, M., Yoshimatsu, K., Azuma, M., Okada, Y., Hitoshi, Y., Yagita, H., Takatsu, K., Komuro, K. J. Immunol. (1995) [Pubmed]
  4. Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. Ding, Z.M., Babensee, J.E., Simon, S.I., Lu, H., Perrard, J.L., Bullard, D.C., Dai, X.Y., Bromley, S.K., Dustin, M.L., Entman, M.L., Smith, C.W., Ballantyne, C.M. J. Immunol. (1999) [Pubmed]
  5. Aggravated Lyme carditis in CD11a-/- and CD11c-/- mice. Guerau-de-Arellano, M., Alroy, J., Bullard, D., Huber, B.T. Infect. Immun. (2005) [Pubmed]
  6. Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway. Moriyama, H., Yokono, K., Amano, K., Nagata, M., Hasegawa, Y., Okamoto, N., Tsukamoto, K., Miki, M., Yoneda, R., Yagi, N., Tominaga, Y., Kikutani, H., Hioki, K., Okumura, K., Yagita, H., Kasuga, M. J. Immunol. (1996) [Pubmed]
  7. A subset of T cell receptors associated with L3T4 molecules mediates C6VL leukemia cell binding of its cognate retrovirus. O'Neill, H.C., McGrath, M.S., Allison, J.P., Weissman, I.L. Cell (1987) [Pubmed]
  8. NK cells promote islet allograft tolerance via a perforin-dependent mechanism. Beilke, J.N., Kuhl, N.R., Van Kaer, L., Gill, R.G. Nat. Med. (2005) [Pubmed]
  9. Sequence homology of the LFA-1 and Mac-1 leukocyte adhesion glycoproteins and unexpected relation to leukocyte interferon. Springer, T.A., Teplow, D.B., Dreyer, W.J. Nature (1985) [Pubmed]
  10. LFA-1 but not Lyt-2 is associated with killing activity of cytotoxic T lymphocyte hybridomas. Kaufmann, Y., Golstein, P., Pierres, M., Springer, T.A., Eshhar, Z. Nature (1982) [Pubmed]
  11. The genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo. Kohl, S., Loo, L.S., Schmalstieg, F.S., Anderson, D.C. J. Immunol. (1986) [Pubmed]
  12. Lymphocyte function-associated antigen 1 (LFA-1) contains sulfated N-linked oligosaccharides. Dahms, N.M., Hart, G.W. J. Immunol. (1985) [Pubmed]
  13. Pertussis toxin inhibition of T-cell hybridoma invasion is reversed by manganese-induced activation of LFA-1. La Rivière, G., Klein Gebbinck, J.W., Driessens, M.H., Roos, E. J. Cell. Sci. (1994) [Pubmed]
  14. Suppression of atopic-like dermatitis by treatment with antibody to lymphocyte function-associated antigen-1 in NC/Nga mouse. Ohmura, T., Konomi, A., Satoh, Y., Hayashi, T., Tsunenari, I., Kadota, T., Panzenbeck, M.J., Satoh, H. Eur. J. Pharmacol. (2004) [Pubmed]
  15. Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1. Sanchez-Madrid, F., Simon, P., Thompson, S., Springer, T.A. J. Exp. Med. (1983) [Pubmed]
  16. The Ly-15 alloantigenic system: a genetically determined polymorphism of the murine lymphocyte function-associated antigen-1 molecule. Hogarth, P.M., Walker, I.D., McKenzie, I.F., Springer, T.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  17. The role of LFA-1/ICAM-1 interactions during murine T lymphocyte development. Fine, J.S., Kruisbeek, A.M. J. Immunol. (1991) [Pubmed]
  18. Differential expression of lymphocyte function-associated antigen 1 (LFA-1) on epidermotropic and non-epidermotropic T-cell clones. Shiohara, T., Moriya, N., Gotoh, C., Hayakawa, J., Saizawa, K., Yagita, H., Nagashima, M. J. Invest. Dermatol. (1989) [Pubmed]
  19. Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue. Nakajima, H., Sano, H., Nishimura, T., Yoshida, S., Iwamoto, I. J. Exp. Med. (1994) [Pubmed]
  20. The use of lymphocyte function-associated antigen (LFA)-1-deficient mice to determine the role of LFA-1, Mac-1, and alpha4 integrin in the inflammatory response of neutrophils. Henderson, R.B., Lim, L.H., Tessier, P.A., Gavins, F.N., Mathies, M., Perretti, M., Hogg, N. J. Exp. Med. (2001) [Pubmed]
  21. The role of LFA-1 (CD11a/CD18) cytoplasmic domains in binding to intercellular adhesion molecule-1 (CD54) and in postreceptor cell spreading. Pyszniak, A.M., Carpenito, C., Takei, F. Exp. Cell Res. (1997) [Pubmed]
  22. A statin-based inhibitor of lymphocyte function antigen-1 protects against ischemia/reperfusion-induced leukocyte adhesion in the colon. Wan, M.X., Schramm, R., Klintman, D., Welzenbach, K., Weitz-Schmidt, G., Thorlacius, H. Br. J. Pharmacol. (2003) [Pubmed]
  23. 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]
  24. LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids. Sadhu, C., Lipsky, B., Erickson, H.P., Hayflick, J., Dick, K.O., Gallatin, W.M., Staunton, D.E. Cell Adhes. Commun. (1994) [Pubmed]
  25. LFA-1-mediated costimulation of CD8+ T cell proliferation requires phosphatidylinositol 3-kinase activity. Ni, H.T., Deeths, M.J., Mescher, M.F. J. Immunol. (2001) [Pubmed]
  26. Ligation of CD3 triggers transmembrane proximity between LFA-1 and cortical microfilaments in a cytotoxic T cell clone derived from tumor infiltrating lymphocytes: a quantitative resonance energy transfer microscopy study. Poo, H., Fox, B.A., Petty, H.R. J. Cell. Physiol. (1994) [Pubmed]
  27. Major histocompatibility complex-restricted antigen receptor on T cells. VIII. Role of the LFA-1 molecule. Golde, W.T., Kappler, J.W., Greenstein, J., Malissen, B., Hood, L., Marrack, P. J. Exp. Med. (1985) [Pubmed]
  28. ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. Wang, H., McCann, F.E., Gordan, J.D., Wu, X., Raab, M., Malik, T.H., Davis, D.M., Rudd, C.E. J. Exp. Med. (2004) [Pubmed]
  29. Control of leukocyte rolling velocity in TNF-alpha-induced inflammation by LFA-1 and Mac-1. Dunne, J.L., Ballantyne, C.M., Beaudet, A.L., Ley, K. Blood (2002) [Pubmed]
  30. Inhibition of epidermal Langerhans cell function by low dose ultraviolet B radiation. Ultraviolet B radiation selectively modulates ICAM-1 (CD54) expression by murine Langerhans cells. Tang, A., Udey, M.C. J. Immunol. (1991) [Pubmed]
  31. Increased resistance of LFA-1-deficient mice to lipopolysaccharide-induced shock/liver injury in the presence of TNF-alpha and IL-12 is mediated by IL-10: a novel role for LFA-1 in the regulation of the proinflammatory and anti-inflammatory cytokine balance. Emoto, M., Emoto, Y., Brinkmann, V., Miyamoto, M., Yoshizawa, I., Stäber, M., van Rooijen, N., Hamann, A., Kaufmann, S.H. J. Immunol. (2003) [Pubmed]
  32. Regulation of leukocyte function-associated antigen 1-mediated adhesion by somatostatin and substance P in mouse spleen cells. Kang, B.N., Kim, H.J., Jeong, K.S., Park, S.J., Kim, S.H., Kim, S.R., Kim, T.H., Ryu, S.Y. Neuroimmunomodulation (2004) [Pubmed]
  33. Cell-to-Cell adhesion via intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 pathway is involved in 1alpha,25(OH)2D3, PTH and IL-1alpha-induced osteoclast differentiation and bone resorption. Okada, Y., Morimoto, I., Ura, K., Watanabe, K., Eto, S., Kumegawa, M., Raisz, L., Pilbeam, C., Tanaka, Y. Endocr. J. (2002) [Pubmed]
  34. Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways. Xu, B., Wagner, N., Pham, L.N., Magno, V., Shan, Z., Butcher, E.C., Michie, S.A. J. Exp. Med. (2003) [Pubmed]
  35. Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice. Berlin-Rufenach, C., Otto, F., Mathies, M., Westermann, J., Owen, M.J., Hamann, A., Hogg, N. J. Exp. Med. (1999) [Pubmed]
  36. The antigen dose determines T helper subset development by regulation of CD40 ligand. Ruedl, C., Bachmann, M.F., Kopf, M. Eur. J. Immunol. (2000) [Pubmed]
  37. Indefinite survival of neonatal porcine islet xenografts by simultaneous targeting of LFA-1 and CD154 or CD45RB. Rayat, G.R., Gill, R.G. Diabetes (2005) [Pubmed]
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