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Gene Review

ITGB2  -  integrin, beta 2 (complement component 3...

Homo sapiens

Synonyms: CD18, Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta, Complement receptor C3 subunit beta, Integrin beta-2, LAD, ...
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Disease relevance of ITGB2

  • Previously, we localized the binding sites of LFA-1 and the major group of human rhinoviruses to the first NH2-terminal immunoglobulin-like domain of ICAM-1 [1].
  • Negative or weak expression of LFA-1 and LFA-3 was also observed in 7 of 8 EBV genome negative BL [2].
  • Involvement of LFA-1/intracellular adhesion molecule-1-dependent cell adhesion in CD40-mediated inhibition of human B lymphoma cell death induced by surface IgM crosslinking [3].
  • Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance [4].
  • Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions [5].

Psychiatry related information on ITGB2


High impact information on ITGB2


Chemical compound and disease context of ITGB2


Biological context of ITGB2

  • Here, we show that the binding site on ICAM-1 for Mac-1 is unexpectedly distinct from that for LFA-1 and maps to the third NH2-terminal immunoglobulin-like domain [1].
  • However, coengagement of 2B4 with LFA-1 resulted in an enhancement of Vav1 phosphorylation that was sensitive to cholesterol depletion and to inhibition of actin polymerization [17].
  • In contrast, LFA-1-mediated cell adhesion and spreading on intercellular cell adhesion molecule 1 is strongly inhibited by a cytohesin-1 mutant, which fails to catalyze ARF GDP-GTP exchange in vitro [18].
  • In addition, inhibitors of tyrosine kinase activity also abolished ICAM-3 and LFA-1-mediated cell aggregation [19].
  • Aggregation occurred with similar kinetics regardless of the presence of phorbol ester or the "activating" monoclonal antibody (MoAb) KIM 185, suggesting that the avidity of LFA-1 is not modulated on NB-4 cells in a manner similar to other leukocytes [20].

Anatomical context of ITGB2

  • We found that JAB1 is present both in the nucleus and in the cytoplasm of cells and that a fraction of JAB1 colocalizes with LFA-1 at the cell membrane [21].
  • Using transfected insect cells that express ligands of human NK cell receptors, we show that engagement of the beta2 integrin LFA-1 on NK cells by intercellular adhesion molecule (ICAM)-1 led to a tyrosine phosphorylation of Vav1 that was not sensitive to cholesterol depletion and to inhibition of actin polymerization [17].
  • This level of expression should be adequate for normal integrin function, but both the patient's Mac-1 on neutrophils and LFA-1 on T cells failed to bind ligands such as fibrinogen and intercellular adhesion molecule (ICAM)-1, respectively, or to display a beta2-integrin activation epitope after adhesion-inducing stimuli [22].
  • Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes [23].
  • Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro [24].

Associations of ITGB2 with chemical compounds

  • Two color fluorescence cell conjugate experiments show that neutrophils stimulated with fMLP bind to HUVEC stimulated with lipopolysaccharide for 24 h in an ICAM-1-, Mac-1-, and LFA-1-dependent fashion [25].
  • Taken together, our findings provide a clinically relevant system for study of LFA-1/ICAM-2 interaction and suggest a mechanism in part for retinoic acid syndrome and the effectiveness of MPSS in ameliorating retinoic acid syndrome [20].
  • We next investigated the function of these adhesion molecules and their ligands, LFA-1, very late activation Ag (WLA-L) and sialylated Lewis x glycoprotein (sLe(x)), in adhesion assays with the monocyte-like cell line U937 [26].
  • Monocytic CD18 was elevated both in the diabetes and in the impaired glucose tolerance groups [4].
  • We determined simultaneously the changes in the granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor during dialysis using a complement activating and a non-complement activating membrane, in a randomized, cross-over study [27].

Physical interactions of ITGB2


Regulatory relationships of ITGB2

  • We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization [21].
  • We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration [23].
  • Secondly, cytohesin-1 induces expression of an extracellular activation epitope of LFA-1, and the exchange factor function is not essential for this activity [18].
  • Studies with specific antibodies showed that monocyte adhesion to platelets was mainly mediated by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). beta2-Integrin blocking CD18 and CD11b antibodies partly inhibited the arrest of rolling cells [32].
  • We found that the cross-linking of CD11b as well as of CD18 induced comparable rapid increases in CD64 expression on the surface of PMNs, occurring within 15 minutes of exposure [33].

Other interactions of ITGB2


Analytical, diagnostic and therapeutic context of ITGB2


  1. Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Diamond, M.S., Staunton, D.E., Marlin, S.D., Springer, T.A. Cell (1991) [Pubmed]
  2. Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus. Billaud, M., Rousset, F., Calender, A., Cordier, M., Aubry, J.P., Laisse, V., Lenoir, G.M. Blood (1990) [Pubmed]
  3. Involvement of LFA-1/intracellular adhesion molecule-1-dependent cell adhesion in CD40-mediated inhibition of human B lymphoma cell death induced by surface IgM crosslinking. Sumimoto, S., Heike, T., Kanazashi, S., Shintaku, N., Jung, E.Y., Hata, D., Katamura, K., Mayumi, M. J. Immunol. (1994) [Pubmed]
  4. Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance. Fogelstrand, L., Hulthe, J., Hultén, L.M., Wiklund, O., Fagerberg, B. Diabetologia (2004) [Pubmed]
  5. Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. Giguère, J.F., Tremblay, M.J. J. Virol. (2004) [Pubmed]
  6. Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions. Buyon, J.P., Slade, S.G., Reibman, J., Abramson, S.B., Philips, M.R., Weissmann, G., Winchester, R. J. Immunol. (1990) [Pubmed]
  7. Acute psychological stress and exercise and changes in peripheral leukocyte adhesion molecule expression and density. Goebel, M.U., Mills, P.J. Psychosomatic medicine. (2000) [Pubmed]
  8. Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family. Rozemuller, J.M., Eikelenboom, P., Pals, S.T., Stam, F.C. Neurosci. Lett. (1989) [Pubmed]
  9. Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Dustin, M.L., Springer, T.A. Annu. Rev. Immunol. (1991) [Pubmed]
  10. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Springer, T.A., Dustin, M.L., Kishimoto, T.K., Marlin, S.D. Annu. Rev. Immunol. (1987) [Pubmed]
  11. Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. Kolanus, W., Nagel, W., Schiller, B., Zeitlmann, L., Godar, S., Stockinger, H., Seed, B. Cell (1996) [Pubmed]
  12. The binding site on ICAM-1 for Plasmodium falciparum-infected erythrocytes overlaps, but is distinct from, the LFA-1-binding site. Berendt, A.R., McDowall, A., Craig, A.G., Bates, P.A., Sternberg, M.J., Marsh, K., Newbold, C.I., Hogg, N. Cell (1992) [Pubmed]
  13. pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression. Serrano, C.V., Fraticelli, A., Paniccia, R., Teti, A., Noble, B., Corda, S., Faraggiana, T., Ziegelstein, R.C., Zweier, J.L., Capogrossi, M.C. Am. J. Physiol. (1996) [Pubmed]
  14. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Hirahashi, J., Mekala, D., Van Ziffle, J., Xiao, L., Saffaripour, S., Wagner, D.D., Shapiro, S.D., Lowell, C., Mayadas, T.N. Immunity (2006) [Pubmed]
  15. Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms. Lo, S.K., Everitt, J., Gu, J., Malik, A.B. J. Clin. Invest. (1992) [Pubmed]
  16. IL-4 induces LFA-1 and LFA-3 expression on Burkitt's lymphoma cell lines. Requirement of additional activation by phorbol myristate acetate for induction of homotypic cell adhesions. Rousset, F., Billaud, M., Blanchard, D., Figdor, C., Lenoir, G.M., Spits, H., De Vries, J.E. J. Immunol. (1989) [Pubmed]
  17. Vav1 phosphorylation is induced by beta2 integrin engagement on natural killer cells upstream of actin cytoskeleton and lipid raft reorganization. Riteau, B., Barber, D.F., Long, E.O. J. Exp. Med. (2003) [Pubmed]
  18. Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1. Geiger, C., Nagel, W., Boehm, T., van Kooyk, Y., Figdor, C.G., Kremmer, E., Hogg, N., Zeitlmann, L., Dierks, H., Weber, K.S., Kolanus, W. EMBO J. (2000) [Pubmed]
  19. Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase. Arroyo, A.G., Campanero, M.R., Sánchez-Mateos, P., Zapata, J.M., Ursa, M.A., del Pozo, M.A., Sánchez-Madrid, F. J. Cell Biol. (1994) [Pubmed]
  20. 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]
  21. Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Bianchi, E., Denti, S., Granata, A., Bossi, G., Geginat, J., Villa, A., Rogge, L., Pardi, R. Nature (2000) [Pubmed]
  22. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. Hogg, N., Stewart, M.P., Scarth, S.L., Newton, R., Shaw, J.M., Law, S.K., Klein, N. J. Clin. Invest. (1999) [Pubmed]
  23. Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium. Schwartz, B.R., Wayner, E.A., Carlos, T.M., Ochs, H.D., Harlan, J.M. J. Clin. Invest. (1990) [Pubmed]
  24. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. Smith, C.W., Marlin, S.D., Rothlein, R., Toman, C., Anderson, D.C. J. Clin. Invest. (1989) [Pubmed]
  25. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). Diamond, M.S., Staunton, D.E., de Fougerolles, A.R., Stacker, S.A., Garcia-Aguilar, J., Hibbs, M.L., Springer, T.A. J. Cell Biol. (1990) [Pubmed]
  26. Differential induction of VCAM-1 on human iliac venous and arterial endothelial cells and its role in adhesion. Hauser, I.A., Johnson, D.R., Madri, J.A. J. Immunol. (1993) [Pubmed]
  27. Modulation of granulocyte LAM-1 and MAC-1 during dialysis--a prospective, randomized controlled trial. Himmelfarb, J., Zaoui, P., Hakim, R. Kidney Int. (1992) [Pubmed]
  28. Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. Luscinskas, F.W., Brock, A.F., Arnaout, M.A., Gimbrone, M.A. J. Immunol. (1989) [Pubmed]
  29. Regulation of adhesion and transendothelial migration of natural killer cells. Allavena, P., Bianchi, G., Paganin, C., Giardina, G., Mantovani, A. Nat. Immun. (1996) [Pubmed]
  30. Cytohesin-1 is a dynamic regulator of distinct LFA-1 functions in leukocyte arrest and transmigration triggered by chemokines. Weber, K.S., Weber, C., Ostermann, G., Dierks, H., Nagel, W., Kolanus, W. Curr. Biol. (2001) [Pubmed]
  31. Exogenous eosinophil activation converts PSGL-1-dependent binding to CD18-dependent stable adhesion to platelets in shear flow. McCarty, O.J., Tien, N., Bochner, B.S., Konstantopoulos, K. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  32. P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions. Kuijper, P.H., Gallardo Torres, H.I., Houben, L.A., Lammers, J.W., Zwaginga, J.J., Koenderman, L. J. Leukoc. Biol. (1998) [Pubmed]
  33. 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]
  34. The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. Sitrin, R.G., Todd, R.F., Albrecht, E., Gyetko, M.R. J. Clin. Invest. (1996) [Pubmed]
  35. Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Liesveld, J.L., Winslow, J.M., Frediani, K.E., Ryan, D.H., Abboud, C.N. Blood (1993) [Pubmed]
  36. Neutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, and VLA-4. Hakkert, B.C., Kuijpers, T.W., Leeuwenberg, J.F., van Mourik, J.A., Roos, D. Blood (1991) [Pubmed]
  37. Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction. Thoma, S.J., Lamping, C.P., Ziegler, B.L. Blood (1994) [Pubmed]
  38. Evidence for an involvement of the neutrophil integrin lymphocyte function-associated antigen-1 in early failure of heart transplants. Oubenaissa, A., Mouas, C., Bourgeois, F., Le Deist, F., Albérici, G., Moalic, J.M., Menasché, P. Circulation (1996) [Pubmed]
  39. 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]
  40. 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]
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