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Gene Review

ITGAL  -  integrin, alpha L (antigen CD11A (p180),...

Homo sapiens

Synonyms: CD11 antigen-like family member A, CD11A, Integrin alpha-L, LFA-1, LFA-1A, ...
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Disease relevance of ITGAL


High impact information on ITGAL

  • The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus [6].
  • The beta2 integrin LFA-1 (lymphocyte function associated antigen; CD11a/CD18) is the common ligand for the intercellular adhesion molecules (ICAMs) [7].
  • Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily [8].
  • Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12) [8].
  • We report the expression cloning of a complementary DNA, pICAM-3, encoding a protein constitutively expressed on all leukocytes, which binds LFA-1 [8].

Chemical compound and disease context of ITGAL


Biological context of ITGAL


Anatomical context of ITGAL

  • Strong evidence indicates that stress-triggered abortion is mediated by adhesion molecules, i.e., intercellular adhesion molecule 1 (ICAM1) and leukocyte function associated molecule 1, now being referred to as integrin alpha L (ITGAL), which facilitate recruitment of inflammatory cells to the feto-maternal interface [18].
  • Immunoblotting studies identified multiple NK cell plasma membrane-associated proteins to be reduced by DTT under LFA-1-activating conditions, but similar effects were also promoted by reducing agent treatments that failed to alter adhesive function [19].
  • Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands [20].
  • The role of leukocyte function-associated Ag-1 (LFA-1) (CD11a/CD18) in T cell-endothelial cell (EC) interactions was assessed by utilizing CD11a/CD18-deficient T cell clones generated from a patient with leukocyte adhesion deficiency (LAD) [21].
  • Murine cell lines bind to purified human LFA-1 through ICAM-1 and at least one other counter-receptor [22].

Associations of ITGAL with chemical compounds

  • Bisulfite sequencing was used to compare methylation patterns in the promoter and 5' flanking regions of the ITGAL gene, encoding CD11a, in normal human T cells, which express LFA-1, and fibroblasts, which do not [14].
  • LFA-1 activation was not because of DTT chelation of Ca2+ or Zn2+ [19].
  • The conformation of LFA-1 alanine mutants was not significantly altered [23].
  • We found that monoclonal antibodies against CD11a, CD11b, CD18, or LW(ab) block adhesion of transfectant L-cells to immobilized ICAM-4-Fc protein and that the ICAM-4/beta(2) integrin interaction was highly sensitive to the presence of the divalent cations Ca(2+) and Mg(2+) [24].
  • Our results suggest that alpha(4) but not LFA-1 integrin avidity stimulation by chemokines involves rapid chemokine-induced GPCR rearrangement that takes place at cholesterol raft platforms upstream to G(i) signaling [25].

Physical interactions of ITGAL


Regulatory relationships of ITGAL


Other interactions of ITGAL


Analytical, diagnostic and therapeutic context of ITGAL

  • However, in the patients with restenosis, the MFI of CD18 significantly increased at 48 h after PTCA (from 57 +/- 6 to 73 +/- 8, p = 0.0008) [37].
  • Both patients share a complete absence of CD18 protein precursor and cell surface expression, but they differ in the level of CD18 mRNA, which is normal in HS and undetectable by Northern blot in ZJO [38].
  • CD11a, CD11b, CD18, and CD35 was studied by flow cytometry on neutrophils and monocytes [39].
  • Sequential immunoprecipitation studies using the CD11a mAb (2F12) also indicate that mNI-58A recognizes an epitope on the alpha-chain of the LFA-1 molecule [40].
  • Examination of T cells from kidney graft fine-needle aspiration biopsies during rejection revealed intragraft accumulation of 'memory'-type T cells expressing high levels of CD2 and LFA-1 (CD11a/CD18) [41].


  1. RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements. Puig-Kröger, A., Sanchez-Elsner, T., Ruiz, N., Andreu, E.J., Prosper, F., Jensen, U.B., Gil, J., Erickson, P., Drabkin, H., Groner, Y., Corbi, A.L. Blood (2003) [Pubmed]
  2. Engagement of adhesion molecules (CD18, CD11a, CD45, CD44, and CD58) enhances human immunodeficiency virus type 1 replication in monocytic cells through a tumor necrosis factor-modulated pathway. Shattock, R.J., Rizzardi, G.P., Hayes, P., Griffin, G.E. J. Infect. Dis. (1996) [Pubmed]
  3. Adhesion molecules in B-chronic lymphoproliferative disorders. Angelopoulou, M.K., Kontopidou, F.N., Pangalis, G.A. Semin. Hematol. (1999) [Pubmed]
  4. Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells. Barker, H.F., Hamilton, M.S., Ball, J., Drew, M., Franklin, I.M. Br. J. Haematol. (1992) [Pubmed]
  5. Engagement of ICAM-1 by major group rhinoviruses activates the LFA-1/ICAM-3 cell adhesion pathway in mononuclear phagocytes. Kirchberger, S., Vetr, H., Majdic, O., Stockinger, H., Stöckl, J. Immunobiology (2006) [Pubmed]
  6. The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus. Staunton, D.E., Dustin, M.L., Erickson, H.P., Springer, T.A. Cell (1990) [Pubmed]
  7. A co-stimulatory signal through ICAM-beta2 integrin-binding potentiates neutrophil phagocytosis. Schnitzler, N., Haase, G., Podbielski, A., Lütticken, R., Schweizer, K.G. Nat. Med. (1999) [Pubmed]
  8. 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]
  9. Adhesion molecules mediating recruitment of monocytes to inflamed tissue. Patarroyo, M. Immunobiology (1994) [Pubmed]
  10. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Lu, Q., Kaplan, M., Ray, D., Ray, D., Zacharek, S., Gutsch, D., Richardson, B. Arthritis Rheum. (2002) [Pubmed]
  11. The leukocyte surface antigens CD11b and CD18 mediate the oxidative burst activation of human peritoneal macrophages induced by type 1 fimbriated Escherichia coli. Gbarah, A., Gahmberg, C.G., Boner, G., Sharon, N. J. Leukoc. Biol. (1993) [Pubmed]
  12. CD11/CD18 leukocyte integrins: new signaling receptors for bacterial endotoxin. Flaherty, S.F., Golenbock, D.T., Milham, F.H., Ingalls, R.R. J. Surg. Res. (1997) [Pubmed]
  13. Effects of methylprednisolone administration on lymphocyte LECAM-1, CD44, and LFA-1 expression. Implications for steroid-induced lymphopenia. Sackstein, R. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  14. Effect of DNA methylation and chromatin structure on ITGAL expression. Lu, Q., Ray, D., Gutsch, D., Richardson, B. Blood (2002) [Pubmed]
  15. Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Zhang, Z., Deng, C., Lu, Q., Richardson, B. Mech. Ageing Dev. (2002) [Pubmed]
  16. 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]
  17. Activation of lymphocyte function-associated molecule-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) mimicked by an antibody directed against CD18. Petruzzelli, L., Maduzia, L., Springer, T.A. J. Immunol. (1995) [Pubmed]
  18. Nerve growth factor translates stress response and subsequent murine abortion via adhesion molecule-dependent pathways. Tometten, M., Blois, S., Kuhlmei, A., Stretz, A., Klapp, B.F., Arck, P.C. Biol. Reprod. (2006) [Pubmed]
  19. Evidence for a dithiol-activated signaling pathway in natural killer cell avidity regulation of leukocyte function antigen-1: structural requirements and relationship to phorbol ester- and CD16-triggered pathways. Edwards, B.S., Curry, M.S., Southon, E.A., Chong, A.S., Graf, L.H. Blood (1995) [Pubmed]
  20. Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands. Lo, S.K., Van Seventer, G.A., Levin, S.M., Wright, S.D. J. Immunol. (1989) [Pubmed]
  21. Role of CD11/CD18 in adhesion and transendothelial migration of T cells. Analysis utilizing CD18-deficient T cell clones. Kavanaugh, A.F., Lightfoot, E., Lipsky, P.E., Oppenheimer-Marks, N. J. Immunol. (1991) [Pubmed]
  22. On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. Johnston, S.C., Dustin, M.L., Hibbs, M.L., Springer, T.A. J. Immunol. (1990) [Pubmed]
  23. Identification of amino acids in the CD11a I-domain important for binding of the leukocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule-1 (ICAM-1). Edwards, C.P., Champe, M., Gonzalez, T., Wessinger, M.E., Spencer, S.A., Presta, L.G., Berman, P.W., Bodary, S.C. J. Biol. Chem. (1995) [Pubmed]
  24. 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]
  25. Chemokine stimulation of lymphocyte alpha 4 integrin avidity but not of leukocyte function-associated antigen-1 avidity to endothelial ligands under shear flow requires cholesterol membrane rafts. Shamri, R., Grabovsky, V., Feigelson, S.W., Dwir, O., Van Kooyk, Y., Alon, R. J. Biol. Chem. (2002) [Pubmed]
  26. 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]
  27. The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin. Tian, L., Yoshihara, Y., Mizuno, T., Mori, K., Gahmberg, C.G. J. Immunol. (1997) [Pubmed]
  28. The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. Bailly, P., Tontti, E., Hermand, P., Cartron, J.P., Gahmberg, C.G. Eur. J. Immunol. (1995) [Pubmed]
  29. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. Béchard, D., Scherpereel, A., Hammad, H., Gentina, T., Tsicopoulos, A., Aumercier, M., Pestel, J., Dessaint, J.P., Tonnel, A.B., Lassalle, P. J. Immunol. (2001) [Pubmed]
  30. 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]
  31. A CD44 monoclonal antibody differentially regulates CD11a/CD18 binding to intercellular adhesion molecules CD54, CD102 and CD50. Vermot-Desroches, C., Wijdenes, J., Valmu, L., Roy, C., Pigott, R., Nortamo, P., Gahmberg, C.G. Eur. J. Immunol. (1995) [Pubmed]
  32. Adhesion molecule-mediated signals regulate major histocompatibility complex-unrestricted and CD3/T cell receptor-triggered cytotoxicity. Galandrini, R., Albi, N., Zarcone, D., Grossi, C.E., Velardi, A. Eur. J. Immunol. (1992) [Pubmed]
  33. 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]
  34. Costimulation via vascular cell adhesion molecule-1 induces in T cells increased responsiveness to the CD28 counter-receptor B7. Damle, N.K., Klussman, K., Leytze, G., Ochs, H.D., Aruffo, A., Linsley, P.S., Ledbetter, J.A. Cell. Immunol. (1993) [Pubmed]
  35. 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]
  36. Human astrocytes are only partially competent antigen presenting cells. Possible implications for lesion development in multiple sclerosis. Weber, F., Meinl, E., Aloisi, F., Nevinny-Stickel, C., Albert, E., Wekerle, H., Hohlfeld, R. Brain (1994) [Pubmed]
  37. 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]
  38. Characterization of two new CD18 alleles causing severe leukocyte adhesion deficiency. López Rodríguez, C., Nueda, A., Grospierre, B., Sánchez-Madrid, F., Fischer, A., Springer, T.A., Corbí, A.L. Eur. J. Immunol. (1993) [Pubmed]
  39. Adherence of human monocytes to haemodialysis membranes: LFA 1 (CD11a/CD18) CR1 (CD35) and CR3 (CD11b/CD18) triggering promotes the biosynthesis of platelet-activating factor and adherence. Tetta, C., Tropea, F., Camussi, G., Neri, R., Wratten, M.L., Sereni, L., Silvestro, L., Franceschi, C., Haeffner-Cavaillon, N. Nephrol. Dial. Transplant. (1995) [Pubmed]
  40. A novel monoclonal antibody mNI-58A against the alpha-chain of leukocyte function-associated antigen-1 (LFA-1) blocks the homotypic cell aggregation and actively regulates morphological changes in the phorbol myristate acetate (PMA)-activated human monocyte-like cell line, U937. Ikewaki, N., Yamada, A., Sonoda, A., Inoko, H. Tissue Antigens (1996) [Pubmed]
  41. Discordant expression of LFA-1, VLA-4alpha, VLA-beta 1, CD45RO and CD28 on T-cell subsets: evidence for multiple subsets of 'memory' T cells. Kern, F., Döcke, W.D., Reinke, P., Volk, H.D. Int. Arch. Allergy Immunol. (1994) [Pubmed]
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