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Gene Review

ITGAM  -  integrin, alpha M (complement component 3...

Homo sapiens

Synonyms: CD11 antigen-like family member B, CD11B, CD11b, CR-3 alpha chain, CR3A, ...
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Disease relevance of ITGAM

  • Recently, we described a case of severe neonatal alloimmune neutropenia (NAIN) caused by an alloantibody against a variant of the CD11b subunit (Mart alloantigen) [1].
  • In this study, a critical non-I-domain binding site for uPAR on CD11b (M25; residues 424-440) is identified by homology with a phage display peptide known to bind uPAR [2].
  • We conclude that the expression of two Fc gamma R (I and III), of the adhesion molecules CD11a and CD11b and of HLA-DR showed particular alterations on monocytes from HIV+ subjects [3].
  • Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87) [4].
  • The percentage of macrophages expressing CD11b (CR3) was significantly increased in patients with active sarcoidosis compared with patients who had inactive disease and control subjects [5].

Psychiatry related information on ITGAM


High impact information on ITGAM


Chemical compound and disease context of ITGAM


Biological context of ITGAM


Anatomical context of ITGAM


Associations of ITGAM with chemical compounds

  • Furthermore, comparison of the CD11b gene structure with that of platelet glycoprotein IIb and Drosophila PS2 suggest how the human leukocyte integrins evolved and dispersed during the course of evolution [23].
  • Unlabeled SZP or beta-glucan also blocked CR3 staining by 11 mAb to C-terminal domain epitopes of CD11b but had no effect on staining by mAb directed to the I-domain [24].
  • 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 [25].
  • ICAM-2, whose two extracellular Ig domains show the highest homology to the two NH2-terminal domains of ICAM-1, has been previously shown to be a ligand for CD11a/CD18 [26].
  • 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+) [27].

Physical interactions of ITGAM


Regulatory relationships of ITGAM

  • A clear inverse relationship was observed in the latter but not the former state, suggesting that ZBP-89 represses CD11b gene expression during the further differentiation of monocytes into macrophages [32].
  • Cross-linking uPAR induced rapid and significant increases in membrane expression of CD11b and increased degranulation (release of beta-glucuronidase and lactoferrin) to a significantly greater degree than cross-linking control Abs [33].
  • Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-kappaB and NF-IL-6 [34].
  • The activated conformation of CD11b as identified by the mAb, CBRM1/5, as well as quantitative surface CD11b expression were up-regulated after IL-5 stimulation [35].
  • Here we show that P1 was able to induce CD11/CD18-dependent adhesion of human T lymphocytes to immobilized, purified ICAM-1, -2, and -3 [36].

Other interactions of ITGAM

  • The alpha d subunit is more closely related to CD11b and CD11c than to CD11a [37].
  • Also, nuclear translocation of NFkappaBin PMN was enhanced after incubation with MPO, as was surface expression of CD11b [38].
  • Previous studies demonstrated that integrin alpha(M)beta(2) (CD11b/18, Mac-1) forms a physical complex with the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes [39].
  • Basal adhesion to unstimulated HUVEC of CDE cultured continuously with IL-5 was comparable (8.62 +/- 1.12% adhesion; P = NS), but neither CD11b expression (50.3 +/- 11.8 MSF; P = NS v control) nor adhesion to HUVEC (6.77 +/- 1.35%; P = NS) was enhanced in these eosinophils after acute stimulation with IL-5 [40].
  • Overexpression of ZBP-89 in the monocyte precursor cell line U937 reduced CD11b promoter-driven luciferase activity when U937 cells were induced to differentiate into monocytelike cells using phorbol esters [32].

Analytical, diagnostic and therapeutic context of ITGAM


  1. Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion. Sachs, U.J., Chavakis, T., Fung, L., Lohrenz, A., Bux, J., Reil, A., Ruf, A., Santoso, S. Blood (2004) [Pubmed]
  2. Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function. Simon, D.I., Wei, Y., Zhang, L., Rao, N.K., Xu, H., Chen, Z., Liu, Q., Rosenberg, S., Chapman, H.A. J. Biol. Chem. (2000) [Pubmed]
  3. Expression patterns of Fc gamma receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals. Locher, C., Vanham, G., Kestens, L., Kruger, M., Ceuppens, J.L., Vingerhoets, J., Gigase, P. Clin. Exp. Immunol. (1994) [Pubmed]
  4. Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). Wong, W.S., Simon, D.I., Rosoff, P.M., Rao, N.K., Chapman, H.A. Immunology (1996) [Pubmed]
  5. Expression of alveolar macrophage adhesion molecules in pulmonary sarcoidosis. Striz, I., Wang, Y.M., Kalaycioglu, O., Costabel, U. Chest (1992) [Pubmed]
  6. Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer's disease. Scali, C., Prosperi, C., Bracco, L., Piccini, C., Baronti, R., Ginestroni, A., Sorbi, S., Pepeu, G., Casamenti, F. Neurobiol. Aging (2002) [Pubmed]
  7. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. Soignet, S.L., Maslak, P., Wang, Z.G., Jhanwar, S., Calleja, E., Dardashti, L.J., Corso, D., DeBlasio, A., Gabrilove, J., Scheinberg, D.A., Pandolfi, P.P., Warrell, R.P. N. Engl. J. Med. (1998) [Pubmed]
  8. Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Lee, J.O., Rieu, P., Arnaout, M.A., Liddington, R. Cell (1995) [Pubmed]
  9. Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. Relman, D., Tuomanen, E., Falkow, S., Golenbock, D.T., Saukkonen, K., Wright, S.D. Cell (1990) [Pubmed]
  10. Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Benimetskaya, L., Loike, J.D., Khaled, Z., Loike, G., Silverstein, S.C., Cao, L., el Khoury, J., Cai, T.Q., Stein, C.A. Nat. Med. (1997) [Pubmed]
  11. Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Hutchings, P., Rosen, H., O'Reilly, L., Simpson, E., Gordon, S., Cooke, A. Nature (1990) [Pubmed]
  12. Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults. Molloy, E.J., O'Neill, A.J., Doyle, B.T., Grantham, J.J., Taylor, C.T., Sheridan-Pereira, M., Fitzpatrick, J.M., Webb, D.W., Watson, R.W. Biol. Neonate (2006) [Pubmed]
  13. Identification of the leukocyte adhesion molecules CD11 and CD18 as receptors for type 1-fimbriated (mannose-specific) Escherichia coli. Gbarah, A., Gahmberg, C.G., Ofek, I., Jacobi, U., Sharon, N. Infect. Immun. (1991) [Pubmed]
  14. Neutrophil adhesion molecules in HIV disease. Moore, D.A., Henderson, D., Gazzard, B.G. Clin. Exp. Immunol. (1998) [Pubmed]
  15. The human immunodeficiency virus type I Tat protein potentiates ethanol-induced neutrophil functional impairment in transgenic mice. Prakash, O., Zhang, P., Xie, M., Ali, M., Zhou, P., Coleman, R., Stoltz, D.A., Bagby, G.J., Shellito, J.E., Nelson, S. Alcohol. Clin. Exp. Res. (1998) [Pubmed]
  16. Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (complement receptor type 3). Arnaout, M.A., Gupta, S.K., Pierce, M.W., Tenen, D.G. J. Cell Biol. (1988) [Pubmed]
  17. The A-domain of beta 2 integrin CR3 (CD11b/CD18) is a receptor for the hookworm-derived neutrophil adhesion inhibitor NIF. Rieu, P., Ueda, T., Haruta, I., Sharma, C.P., Arnaout, M.A. J. Cell Biol. (1994) [Pubmed]
  18. The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression. Shelley, C.S., Arnaout, M.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  19. Isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. Bosch, P., Pratt, S.L., Stice, S.L. Biol. Reprod. (2006) [Pubmed]
  20. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). Simon, D.I., Chen, Z., Xu, H., Li, C.Q., Dong, J., McIntire, L.V., Ballantyne, C.M., Zhang, L., Furman, M.I., Berndt, M.C., López, J.A. J. Exp. Med. (2000) [Pubmed]
  21. Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system requiring CD11b/CD18-ICAM-1 adherence. Entman, M.L., Youker, K., Shoji, T., Kukielka, G., Shappell, S.B., Taylor, A.A., Smith, C.W. J. Clin. Invest. (1992) [Pubmed]
  22. 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]
  23. Structural analysis of the CD11b gene and phylogenetic analysis of the alpha-integrin gene family demonstrate remarkable conservation of genomic organization and suggest early diversification during evolution. Fleming, J.C., Pahl, H.L., Gonzalez, D.A., Smith, T.F., Tenen, D.G. J. Immunol. (1993) [Pubmed]
  24. Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). Thornton, B.P., Vĕtvicka, V., Pitman, M., Goldman, R.C., Ross, G.D. J. Immunol. (1996) [Pubmed]
  25. 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]
  26. Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain. Xie, J., Li, R., Kotovuori, P., Vermot-Desroches, C., Wijdenes, J., Arnaout, M.A., Nortamo, P., Gahmberg, C.G. J. Immunol. (1995) [Pubmed]
  27. 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]
  28. Function of the lectin domain of Mac-1/complement receptor type 3 (CD11b/CD18) in regulating neutrophil adhesion. Xia, Y., Borland, G., Huang, J., Mizukami, I.F., Petty, H.R., Todd, R.F., Ross, G.D. J. Immunol. (2002) [Pubmed]
  29. Association of BAP31 with CD11b/CD18. Potential role in intracellular trafficking of CD11b/CD18 in neutrophils. Zen, K., Utech, M., Liu, Y., Soto, I., Nusrat, A., Parkos, C.A. J. Biol. Chem. (2004) [Pubmed]
  30. Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation. El-Ghmati, S.M., Arredouani, M., Van Hoeyveld, E.M., Ceuppens, J.L., Stevens, E.A. Scand. J. Immunol. (2002) [Pubmed]
  31. Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18. Troelstra, A., de Graaf-Miltenburg, L.A., van Bommel, T., Verhoef, J., Van Kessel, K.P., Van Strijp, J.A. J. Immunol. (1999) [Pubmed]
  32. The zinc finger transcription factor ZBP-89 is a repressor of the human beta 2-integrin CD11b gene. Park, H., Shelley, C.S., Arnaout, M.A. Blood (2003) [Pubmed]
  33. Clustering of urokinase receptors (uPAR; CD87) induces proinflammatory signaling in human polymorphonuclear neutrophils. Sitrin, R.G., Pan, P.M., Harper, H.A., Todd, R.F., Harsh, D.M., Blackwood, R.A. J. Immunol. (2000) [Pubmed]
  34. Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro. Nakashima, Y., Sun, D.H., Trindade, M.C., Maloney, W.J., Goodman, S.B., Schurman, D.J., Smith, R.L. The Journal of bone and joint surgery. American volume. (1999) [Pubmed]
  35. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. Zhu, X., Muñoz, N.M., Kim, K.P., Sano, H., Cho, W., Leff, A.R. J. Immunol. (1999) [Pubmed]
  36. ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity. Kotovuori, A., Pessa-Morikawa, T., Kotovuori, P., Nortamo, P., Gahmberg, C.G. J. Immunol. (1999) [Pubmed]
  37. 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]
  38. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Lau, D., Mollnau, H., Eiserich, J.P., Freeman, B.A., Daiber, A., Gehling, U.M., Brümmer, J., Rudolph, V., Münzel, T., Heitzer, T., Meinertz, T., Baldus, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  39. Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration. Pluskota, E., Soloviev, D.A., Plow, E.F. Blood (2003) [Pubmed]
  40. Effect of interleukin-5 exposure during in vitro eosinophilopiesis on MAC-1 adhesion molecule expression and function on cultured human eosinophils. Hamann, K.J., Neeley, S.P., Dowling, T.L., Grant, J.A., Leff, A.R. Blood (1996) [Pubmed]
  41. Camptothecin induces differentiation and stimulates the expression of differentiation-related genes in U-937 human promonocytic leukemia cells. Aller, P., Rius, C., Mata, F., Zorrilla, A., Cabañas, C., Bellón, T., Bernabeu, C. Cancer Res. (1992) [Pubmed]
  42. Heterogeneous populations of class II MHC+ cells in human dermal cell suspensions. Identification of a small subset responsible for potent dermal antigen-presenting cell activity with features analogous to Langerhans cells. Meunier, L., Gonzalez-Ramos, A., Cooper, K.D. J. Immunol. (1993) [Pubmed]
  43. Phenotypic characterization of T cells in bronchoalveolar lavage fluid (BALF) and peripheral blood of patients with diffuse panbronchiolitis; the importance of cytotoxic T cells. Kawakami, K., Kadota, J., Iida, K., Fujii, T., Shirai, R., Matsubara, Y., Kohno, S. Clin. Exp. Immunol. (1997) [Pubmed]
  44. The CD11/CD18 (beta2) integrins modulate neutrophil caspase activation and survival following TNF-alpha or endotoxin induced transendothelial migration. Yan, S.R., Sapru, K., Issekutz, A.C. Immunol. Cell Biol. (2004) [Pubmed]
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