integrin alphaxbeta2

Summary

Summary: A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.

Top Publications

  1. Zang Q, Springer T. Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta2 subunit that restrain activation of the integrin alpha(X)beta(2). J Biol Chem. 2001;276:6922-9 pubmed
    ..The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding. ..
  2. Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer T. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006;25:583-94 pubmed
    ..The results establish an intimate relationship between extension of beta(2) integrins and their activation in immune responses and leukocyte trafficking. ..
  3. Chen X, Yu Y, Mi L, Walz T, Springer T. Molecular basis for complement recognition by integrin ?X?2. Proc Natl Acad Sci U S A. 2012;109:4586-91 pubmed publisher
    ..X)?(2) binds through the ?(X) ?I domain, on the face known to bear the metal ion-dependent adhesion site, at the opposite end of the ?I domain from its site of insertion in the ?-propeller domain. ..
  4. Chen X, Xie C, Nishida N, Li Z, Walz T, Springer T. Requirement of open headpiece conformation for activation of leukocyte integrin alphaXbeta2. Proc Natl Acad Sci U S A. 2010;107:14727-32 pubmed publisher
    ..Intermediate integrin affinity appears to result not from a single conformational state, but from a mixture of equilibrating conformational states. ..
  5. Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer T. Structure of an integrin with an alphaI domain, complement receptor type 4. EMBO J. 2010;29:666-79 pubmed publisher
    ..Differences among 10 molecules in crystal lattices provide unprecedented information on interdomain flexibility important for modelling integrin extension and activation. ..
  6. Bendriss Vermare N, Barthelemy C, Durand I, Bruand C, Dezutter Dambuyant C, Moulian N, et al. Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+), and mature interdigitating dendritic cells. J Clin Invest. 2001;107:835-44 pubmed
    ..The detection of Spi-B mRNA, not only upon in vitro maturation of pDCs, but also in freshly purified IDCs, suggests that in vivo pDCs may differentiate into IDCs. ..
  7. Bauer M, Redecke V, Ellwart J, Scherer B, Kremer J, Wagner H, et al. Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells. J Immunol. 2001;166:5000-7 pubmed
    ..Taken together, these results suggest that within a DC subset a multiplicity of responses can be generated by distinct environmental stimuli and that responses to a given stimulus may be dissimilar between DC subsets. ..
  8. Tang R, Law S, Tan S. Selective recruitment of src family kinase Hck by leukocyte integrin alphaMbeta2 but not alphaLbeta2 or alphaXbeta2. FEBS Lett. 2006;580:4435-42 pubmed
    ..Co-capping was recovered by alpha(L) or alpha(X) cytoplasmic tail truncation or forced separation of the alpha and beta cytoplasmic tails via salt-bridge disruption. ..
  9. Vorup Jensen T, Carman C, Shimaoka M, Schuck P, Svitel J, Springer T. Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alphaXbeta2. Proc Natl Acad Sci U S A. 2005;102:1614-9 pubmed
    ..The observations suggest that the pericellular proteolysis at the leading edge of neutrophils not only facilitates passage through the extracellular matrix but also manufactures binding sites for alphaXbeta2. ..

More Information

Publications62

  1. Lu C, Ferzly M, Takagi J, Springer T. Epitope mapping of antibodies to the C-terminal region of the integrin beta 2 subunit reveals regions that become exposed upon receptor activation. J Immunol. 2001;166:5629-37 pubmed
    ..We thus define five different beta(2) stalk subregions, mAb binding to which correlates with effect on activation, and define regions in an interface that becomes exposed upon integrin activation. ..
  2. Brocker T, Gulbranson Judge A, Flynn S, Riedinger M, Raykundalia C, Lane P. CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles. Eur J Immunol. 1999;29:1610-6 pubmed
    ..This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells. ..
  3. Nockher W, Wiemer J, Scherberich J. Haemodialysis monocytopenia: differential sequestration kinetics of CD14+CD16+ and CD14++ blood monocyte subsets. Clin Exp Immunol. 2001;123:49-55 pubmed
    ..This sequestration kinetics may be due to a distinct surface expression of major adhesion receptors which facilitate leucocyte-leucocyte, as well as leucocyte-endothelial, interactions. ..
  4. Page G, Lebecque S, Miossec P. Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium. J Immunol. 2002;168:5333-41 pubmed
    ..The role of DC in disease initiation and perpetuation makes chemokines involved in DC migration a potential therapeutic target. ..
  5. Kirkitadze M, Barlow P. Structure and flexibility of the multiple domain proteins that regulate complement activation. Immunol Rev. 2001;180:146-61 pubmed
    ..The results could have implications for folding, evolution, flexibility and structure-function relationships of other molecules in the large, diverse and little understood category of multiple domain proteins. ..
  6. Watarai M, Miwa H, Shikami M, Sugamura K, Wakabayashi M, Satoh A, et al. Expression of endothelial cell-associated molecules in AML cells. Leukemia. 2002;16:112-9 pubmed
  7. Barbe L, Boval B, Wautier M, Wautier J. An in vitro system for testing leucocyte and leukaemic cell line adhesion to synthetic fibres. Br J Haematol. 2001;115:664-71 pubmed
    ..Lymphocytes or lymphocytic cell lines were poorly adherent to PET fibres. The retaining capacity of leucocyte filters can be improved by taking into account the different parameters for the design of new filters ..
  8. Aucouturier P, Geissmann F, Damotte D, Saborio G, Meeker H, Kascsak R, et al. Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest. 2001;108:703-8 pubmed
    ..These results suggest that CD11c(+) dendritic cells can propagate prions from the periphery to the CNS in the absence of any additional lymphoid element. ..
  9. Postigo A, Corbi A, Sanchez Madrid F, de Landazuri M. Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18. J Exp Med. 1991;174:1313-22 pubmed
    ..Our data conclusively demonstrate the role of CD11c/CD18 on both B cell activation and adhesion processes. ..
  10. Soumelis V, Scott I, Gheyas F, Bouhour D, Cozon G, Cotte L, et al. Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood. 2001;98:906-12 pubmed
    ..Blood. 2001;98:906-912) ..
  11. Shibahara T, Si Tahar M, Shaw S, Madara J. Adhesion molecules expressed on homing lymphocytes in model intestinal epithelia. Gastroenterology. 2000;118:289-98 pubmed
    ..Flow cytometric screening of adhesion molecules revealed that homed lymphocytes expressed high levels of integrin alphaXbeta2 and alphaEbeta7 and low levels of alpha4beta7 compared with non-homed lymphocytes...
  12. Idres N, Benoit G, Flexor M, Lanotte M, Chabot G. Granulocytic differentiation of human NB4 promyelocytic leukemia cells induced by all-trans retinoic acid metabolites. Cancer Res. 2001;61:700-5 pubmed
  13. Ishikawa S, Nagai S, Sato T, Akadegawa K, Yoneyama H, Zhang Y, et al. Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC. Eur J Immunol. 2002;32:1881-7 pubmed
    ..Since TNF-alpha expression is increased in aged BWF1 mice, DC recruitment in the circulation and maturation into BLC-producing DC by TNF-alpha may play a pivotal role in the development of systemic autoimmune diseases. ..
  14. Dolmer K, Gettins P. Three complement-like repeats compose the complete alpha2-macroglobulin binding site in the second ligand binding cluster of the low density lipoprotein receptor-related protein. J Biol Chem. 2006;281:34189-96 pubmed
  15. Kinashi T. Adhere upright: a switchblade-like extension of beta2 integrins. Immunity. 2006;25:521-2 pubmed
  16. Weis J, Toothaker L, Smith J, Weis J, Fearon D. Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins. J Exp Med. 1988;167:1047-66 pubmed
    ..The homology between CR2 and CR1 extended to the transmembrane and cytoplasmic regions, suggesting that these sequences were derived from a common membrane-bound precursor. ..
  17. Tabibzadeh S. Proliferative activity of lymphoid cells in human endometrium throughout the menstrual cycle. J Clin Endocrinol Metab. 1990;70:437-43 pubmed
    ..The findings suggest that in situ proliferation is one mechanism by which the endometrial lymphoid cell pool within endometrium is restored after each menstrual shedding. ..
  18. Julia V, Hessel E, Malherbe L, Glaichenhaus N, O GARRA A, Coffman R. A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure. Immunity. 2002;16:271-83 pubmed
    ..Taken together, our results may explain the chronic Th2 airway inflammation characteristic of allergic asthma. ..
  19. Heidari M, Harp J, Kehrli M. Expression, purification, and in vitro biological activities of recombinant bovine granulocyte-colony stimulating factor. Vet Immunol Immunopathol. 2001;81:45-57 pubmed
    ..These findings indicate that recombinant bG-CSF (rbG-CSF) expressed in E. coli is biologically active and exerts the same type of effects on neutrophils in vitro as those of human G-CSF (hG-CSF). ..
  20. Koster A, Chew D, Kuebler W, Habazettl H, Bauer M, Hausmann H, et al. Effects of tirofiban on hemostatic activation and inflammatory response during cardiopulmonary bypass. Am J Cardiol. 2003;91:346-7 pubmed
  21. Pittoni V, Valesini G. The clearance of apoptotic cells: implications for autoimmunity. Autoimmun Rev. 2002;1:154-61 pubmed
    ..Impaired clearance of apoptotic cells or the presence of 'danger' signals may modify the balance between tolerance induction and activation of T cells leading to an effective autoimmune response. ..
  22. Jones H, Strid J, Osman M, Uronen Hansson H, Dixon G, Klein N, et al. The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis. Cell Microbiol. 2008;10:1634-45 pubmed publisher
    ..These results reveal a critical role of CR3 and LBP in the phagocytosis of Nm and provide important insights into the initial interaction meningococci have with the immune system. ..
  23. Talamas Rohana P, Wright S, Lennartz M, Russell D. Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins. J Immunol. 1990;144:4817-24 pubmed
    ..Antibody inhibition experiments and competition binding studies with synthetic peptides and soluble LPG indicated that LPG is recognized by the nonpeptide, or "LPS" binding site on CR3. ..
  24. Damoiseaux J, Döpp E, Neefjes J, Beelen R, Dijkstra C. Heterogeneity of macrophages in the rat evidenced by variability in determinants: two new anti-rat macrophage antibodies against a heterodimer of 160 and 95 kd (CD11/CD18). J Leukoc Biol. 1989;46:556-64 pubmed
    ..The new MoAbs ED4, ED7, ED8, and ED9 recognize granulocytes and other unrelated cell types, as well as cells of the mononuclear phagocyte system. ED7 and ED8 recognize a surface heterodimer of Mr 160,000 and 95,000. ..
  25. Kaidoh T, Natsuume Sakai S, Takahashi M. Murine binding protein of the fourth component of complement: structural polymorphism and its linkage to the major histocompatibility complex. Proc Natl Acad Sci U S A. 1981;78:3794-8 pubmed
    ..The recombination frequency between the C4-Bp locus and the S region was 0.017. By phenotyping appropriate intra-H-2 recombinants of three different backgrounds (B10, A, and HT), this locus was assigned to the right of the H-2D region. ..
  26. Koss A, Lucero G, Koziner B. Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor and interleukin 4 induce differentiation in the U-937 human monocytic leukemia cell line. Leuk Lymphoma. 1996;22:163-71,follow.186,color plate XIV-V pubmed
    ..These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures. ..
  27. Lahti M, Heino J, Kapyla J. Leukocyte integrins ?L?2, ?M?2 and ?X?2 as collagen receptors--receptor activation and recognition of GFOGER motif. Int J Biochem Cell Biol. 2013;45:1204-11 pubmed publisher
    ..In brief, leukocyte ?2 integrins may act as collagen receptors in a heterodimer specific manner. ..
  28. Aractingi S, Briand N, Le Danff C, Viguier M, Bachelez H, Michel L, et al. HLA-G and NK receptor are expressed in psoriatic skin: a possible pathway for regulating infiltrating T cells?. Am J Pathol. 2001;159:71-7 pubmed
    ..The demonstration of HLA-G and ILT2 expression in psoriatic skin suggests that this pathway may act as an inhibitory feed back aimed to down-regulate the deleterious effects of T-cell infiltrate in this disease. ..
  29. Yoon J, Pahl M, Vaziri N. Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease. Kidney Int. 2007;71:167-72 pubmed
    ..Thus, this study provides direct evidence of spontaneous leukocyte activation and increased ROS generation (hence the link between oxidative stress and inflammation) in ESRD patients. ..
  30. Lee M, Kweon S, Ha K, Nham S. Fibrin stimulates microfilament reorganization and IL-1beta production in human monocytic THP-1 cells. Mol Cells. 2001;11:13-20 pubmed
  31. Griffin M, Lutz W, Phan V, Bachman L, McKean D, Kumar R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun. 2000;270:701-8 pubmed
    ..Inhibition of DC maturation and stimulatory function was absent in cultures from mice genetically lacking vitamin D receptors (VDR). Vitamin D analogs effectively reduce DC function via VDR-dependent pathways. ..
  32. Gafa V, Manches O, Pastor A, Drouet E, Ambroise Thomas P, Grillot R, et al. Human cytomegalovirus downregulates complement receptors (CR3, CR4) and decreases phagocytosis by macrophages. J Med Virol. 2005;76:361-6 pubmed
    ..These results suggest a new mechanism implicated in the augmentation of opportunistic infections in HCMV patients. ..
  33. Lopez Rodriguez C, Zubiaur M, Sancho J, Concha A, Corbi A. An octamer element functions as a regulatory element in the differentiation-responsive CD11c integrin gene promoter: OCT-2 inducibility during myelomonocytic differentiation. J Immunol. 1997;158:5833-40 pubmed
  34. Ito T, Inaba M, Inaba K, Toki J, Sogo S, Iguchi T, et al. A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. J Immunol. 1999;163:1409-19 pubmed
    ..Furthermore, CD14+ monocytes only expressed E-cadherin, but lacked the other LC markers after culture in these cytokines. Therefore, CD1a+/CD11c+ DCs are the direct precursors of LCs in peripheral blood. ..
  35. Summers K, Hock B, McKenzie J, Hart D. Phenotypic characterization of five dendritic cell subsets in human tonsils. Am J Pathol. 2001;159:285-95 pubmed
    ..The definition and extensive phenotypic analysis of these five DC subsets in human tonsil extends our understanding of the complexity of DC biology. ..
  36. Bellon T, Lopez Rodriguez C, Rubio M, Jochems G, Bernabeu C, Corbi A. Regulated expression of p150,95 (CD11c/CD18; alpha X/beta 2) and VLA-4 (CD49d/CD29; alpha 4/beta 1) integrins during myeloid cell differentiation. Eur J Immunol. 1994;24:41-7 pubmed
  37. Benton L, Purohit U, Khan M, Greco R. The biologic role of B2 integrins in the host response to expanded polytetrafluoroethylene. J Surg Res. 1996;64:116-9 pubmed
    ..This is also true in vivo since PBL increase CD11b expression four times when ePTFE is compared to sham. These observations indicate a potential role in vivo for B2 integrins in vascular prosthetic infections. ..
  38. Doepper S, Kacani L, Falkensammer B, Dierich M, Stoiber H. Complement receptors in HIV infection. Curr Mol Med. 2002;2:703-11 pubmed
  39. Throsby M, Herbelin A, Pleau J, Dardenne M. CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion. J Immunol. 2000;165:1965-75 pubmed
    ..Our data demonstrate a temporal and spatial association between eosinophil recruitment and class I-restricted selection in the thymus, suggesting an immunomodulatory role for eosinophils under nonpathological conditions. ..
  40. van de Poel R, Meijers J, Bouma B. C4b-binding protein inhibits the factor V-dependent but not the factor V-independent cofactor activity of protein S in the activated protein C-mediated inactivation of factor VIIIa. Thromb Haemost. 2001;85:761-5 pubmed
    ..We conclude that C4BP-bound protein S retains its cofactor activity to APC in the factor VIIIa inactivation. ..
  41. Lu R, Pitha P. Monocyte differentiation to macrophage requires interferon regulatory factor 7. J Biol Chem. 2001;276:45491-6 pubmed
    ..The identification of IRF-7 as a key regulator in monocyte differentiation suggests a novel function of IRF-7 in innate immunity. ..
  42. Walker L, Gulbranson Judge A, Flynn S, Brocker T, Raykundalia C, Goodall M, et al. Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J Exp Med. 1999;190:1115-22 pubmed
    ..These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation. ..
  43. Langeggen H, Berge K, Johnson E, Hetland G. Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. Inflammation. 2002;26:103-10 pubmed
    ..The presence of CR1 (CD35) and CR4 (CD1c/CD18) on HUVEC indicates that endothelial cells (EC) have the potential to bind C3b and iC3b, respectively, which both mediate biological effects in the course of complement activation. ..
  44. Noti J, Reinemann B, Petrus M. Sp1 binds two sites in the CD11c promoter in vivo specifically in myeloid cells and cooperates with AP1 to activate transcription. Mol Cell Biol. 1996;16:2940-50 pubmed
    ..We propose that myeloid-specific expression of the CD11c promoter and is facilitated by cooperative interaction between the Sp1- and Ap1-binding sites. ..
  45. Choi J, Nham S. Loops within the CD11c I domain critical for specific recognition of fibrinogen. Biochem Biophys Res Commun. 2002;292:756-60 pubmed
  46. Sen M, Yuki K, Springer T. An internal ligand-bound, metastable state of a leukocyte integrin, ?X?2. J Cell Biol. 2013;203:629-42 pubmed publisher
    ..Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness. ..
  47. Skoberne M, Somersan S, Almodovar W, Truong T, Petrova K, Henson P, et al. The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function. Blood. 2006;108:947-55 pubmed
    ..Overall, our data suggest that under steady-state conditions, signaling via CRs predominates to render DCs tolerogenic. ..
  48. Theimer C, Feigon J. Structure and function of telomerase RNA. Curr Opin Struct Biol. 2006;16:307-18 pubmed
    ..thermophila TERT have been determined. Phylogenetic and biochemical analyses of yeast TERs have revealed core structural elements in common with ciliates and vertebrates, and the minimal domains required for function in vivo...
  49. Berggård K, Johnsson E, Morfeldt E, Persson J, Stålhammar Carlemalm M, Lindahl G. Binding of human C4BP to the hypervariable region of M protein: a molecular mechanism of phagocytosis resistance in Streptococcus pyogenes. Mol Microbiol. 2001;42:539-51 pubmed
    ..This study provides the first molecular insight into the mechanisms by which the HVR of an M protein confers phagocytosis resistance. ..
  50. Schack L, Stapulionis R, Christensen B, Kofod Olsen E, Skov Sørensen U, Vorup Jensen T, et al. Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin. J Immunol. 2009;182:6943-50 pubmed publisher
    ..Taken together, these data identify the alpha(X)beta(2) integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN. ..
  51. Jones G, Watera C, Patterson S, Rutebemberwa A, Kaleebu P, Whitworth J, et al. Comparative loss and maturation of peripheral blood dendritic cell subpopulations in African and non-African HIV-1-infected patients. AIDS. 2001;15:1657-63 pubmed
    ..There was no selective loss of either DC subpopulation, suggesting that the ability of DC to acquire and present antigens or to produce interferon-alpha may both be impaired in HIV-1 infection. ..
  52. Wormsley S, Baird S, Gadol N, Rai K, Sobol R. Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes. Blood. 1990;76:123-30 pubmed
    ..In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias. ..
  53. Borras F, Matthews N, Lowdell M, Navarrete C. Identification of both myeloid CD11c+ and lymphoid CD11c- dendritic cell subsets in cord blood. Br J Haematol. 2001;113:925-31 pubmed
    ..The significance of the inverted CD11c+/CD11c- ratio observed in CB DCs (1:3) with respect to adult blood DCs (3:1) remains to be explained. ..