integrin alpha4beta1

Summary

Summary: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.

Top Publications

  1. ncbi Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1
    C Berlin
    Department of Pathology, Stanford University, California 94305
    Cell 74:185-95. 1993
  2. ncbi Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors
    Hui Jin
    John and Rebecca Moores Comprehensive Cancer Center, University of California at San Diego, San Diego, California, USA
    Cancer Res 66:2146-52. 2006
  3. ncbi Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale
    George P A Rice
    Department of Clinical Neurologic Sciences, University of Western Ontario, London Health Sciences Centre, University Campus, 339 Windermere Road, London, Ontario, Canada N6A 5A5
    Neurology 64:1336-42. 2005
  4. ncbi Paxillin selectively associates with constitutive and chemoattractant-induced high-affinity alpha4beta1 integrins: implications for integrin signaling
    Sharon J Hyduk
    Toronto General Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    Blood 104:2818-24. 2004
  5. ncbi From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial integrin ligands and chemokines at sub-second contacts
    Ronen Alon
    Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
    Semin Immunol 14:93-104. 2002
  6. ncbi The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
    A Peled
    Departments of Immunology and Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Blood 95:3289-96. 2000
  7. ncbi High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers
    Martin Klemke
    Institute for Immunology, University of Heidelberg, Heidelberg, Germany
    J Cell Physiol 212:368-74. 2007
  8. ncbi The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans
    Fabian Zohren
    Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine University, Dusseldorf, Germany
    Blood 111:3893-5. 2008
  9. pmc Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
    Sci Signal 2:ra51. 2009
  10. ncbi Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells
    Norman Putzki
    Department of Neurology, University Clinic Essen, University of Duisburg Essen, Essen, Germany norman putzki kssg ch
    Eur Neurol 63:311-7. 2010

Detail Information

Publications285 found, 100 shown here

  1. ncbi Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1
    C Berlin
    Department of Pathology, Stanford University, California 94305
    Cell 74:185-95. 1993
    ..Alpha 4 beta 7 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a selective role for the interaction of alpha 4 beta 7 and MAdCAM-1 lymphocyte in homing to mucosal sites...
  2. ncbi Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors
    Hui Jin
    John and Rebecca Moores Comprehensive Cancer Center, University of California at San Diego, San Diego, California, USA
    Cancer Res 66:2146-52. 2006
    ..Here, we show that integrin alpha4beta1 (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization...
  3. ncbi Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale
    George P A Rice
    Department of Clinical Neurologic Sciences, University of Western Ontario, London Health Sciences Centre, University Campus, 339 Windermere Road, London, Ontario, Canada N6A 5A5
    Neurology 64:1336-42. 2005
    ..The authors discuss the mechanisms by which alpha4 integrins alter lymphocyte function as a rationale for anti-alpha4 integrin use in MS...
  4. ncbi Paxillin selectively associates with constitutive and chemoattractant-induced high-affinity alpha4beta1 integrins: implications for integrin signaling
    Sharon J Hyduk
    Toronto General Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    Blood 104:2818-24. 2004
    ..These data suggest that ligand binding to high-affinity alpha4beta1 integrins may initiate outside-in signaling cascades through paxillin that regulate leukocyte maturation and emigration...
  5. ncbi From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial integrin ligands and chemokines at sub-second contacts
    Ronen Alon
    Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
    Semin Immunol 14:93-104. 2002
    ..We discuss potential regulatory mechanisms by which a given set of chemokine receptors and integrins may interact to rapidly generate high avidity, shear-resistant integrin-mediated leukocyte arrest on vascular endothelium...
  6. ncbi The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
    A Peled
    Departments of Immunology and Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Blood 95:3289-96. 2000
    ..Our results demonstrate that repopulating human stem cells functionally express LFA-1, VLA-4, and VLA-5. Furthermore, this study implies a novel approach to further advance clinical transplantation...
  7. ncbi High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers
    Martin Klemke
    Institute for Immunology, University of Heidelberg, Heidelberg, Germany
    J Cell Physiol 212:368-74. 2007
    ..Moreover, we demonstrate that function-blocking antibodies against the integrin alpha4beta1, as well as siRNA-mediated knock-down of the alpha4 subunit in these highly metastatic human melanoma cells ..
  8. ncbi The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans
    Fabian Zohren
    Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine University, Dusseldorf, Germany
    Blood 111:3893-5. 2008
    ..001), including pluripotent cells in colony-forming assays. This mobilizing ability of natalizumab might be useful for patients with poor response to granulocyte colony-stimulating factor (G-CSF)-based protocols...
  9. pmc Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
    Sci Signal 2:ra51. 2009
    ..This proteomics workflow now opens the way to further dissection and systems-level analyses of adhesion signaling...
  10. ncbi Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells
    Norman Putzki
    Department of Neurology, University Clinic Essen, University of Duisburg Essen, Essen, Germany norman putzki kssg ch
    Eur Neurol 63:311-7. 2010
    ..Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance...
  11. ncbi Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma
    K Noborio-Hatano
    Division of Hematology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
    Oncogene 28:231-42. 2009
    ..These results suggest that VLA-4 plays a critical role in CAM-DR of MM cells. The combination of bortezomib with conventional anti-myeloma drugs may be effective in overcoming CAM-DR of MM...
  12. ncbi VLA-4-dependent myeloma cell adhesion
    F Sanz-Rodriguez
    Centro de Investigaciones Biologicas, Departamento de Inmunología Velázquez 144, 28006 Madrid, Spain
    Leuk Lymphoma 41:239-45. 2001
    ..In addition, we also speculate on the signalling generated upon interaction of myeloma VLA-4 with its ligands on the survival of these cells in the bone marrow...
  13. ncbi Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia
    Takuya Matsunaga
    Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1, West 16, Chuo Ku, Sapporo 060 0061, Japan
    Nat Med 9:1158-65. 2003
    ..4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis...
  14. pmc Natalizumab and progressive multifocal leukoencephalopathy: what are the causal factors and can it be avoided?
    Clemens Warnke
    Neurology Section, VA North Texas Health Care System, Medical Service, 4500 S Lancaster Rd, Dallas, TX 75216, USA
    Arch Neurol 67:923-30. 2010
    ..In addition, recent data indicate that risk of PML might increase beyond 24 months of treatment...
  15. pmc Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion
    Jacob Rullo
    Toronto General Research Institute, University Health Network, Toronto, M5G 2C4 Ontario, Canada
    J Cell Biol 197:115-29. 2012
    ..These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces...
  16. ncbi Mechanism of CD47-induced alpha4beta1 integrin activation and adhesion in sickle reticulocytes
    Julia E Brittain
    Department of Pharmacology, University of North Carolina at Chapel Hill, 27599 7365, USA
    J Biol Chem 279:42393-402. 2004
    ..These studies therefore identify the alpha4beta1 integrin on SS RBCs as a CD47-activated receptor for TSP, VCAM-1, and plasma fibronectin, revealing novel binding characteristics of this integrin...
  17. ncbi Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29)
    B A Mannion
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 157:2039-47. 1996
    ..Thus, CD81 and other transmembrane-4 superfamily members may participate in functionally relevant interactions with alpha 4 beta 1 and other integrins...
  18. pmc Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth
    Michael C Schmid
    Moores UCSD Cancer Center, University of California, San Diego, California, USA
    Cancer Res 71:6965-75. 2011
    ..These results show that targeting myeloid cell recruitment mechanisms can be an effective approach to suppress tumor progression...
  19. ncbi Evidence for cell adhesion-mediated drug resistance of multiple myeloma cells in vivo
    R Schmidmaier
    Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universitat Munchen, Munchen, Germany
    Int J Biol Markers 21:218-22. 2006
    ..To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry...
  20. ncbi The solution structure of EMILIN1 globular C1q domain reveals a disordered insertion necessary for interaction with the alpha4beta1 integrin
    Giuliana Verdone
    Dipartimento di Scienze e Tecnologie Biomediche, Centro di Eccellenza MATI, Universita di Udine, 33100 Udine, Italy
    J Biol Chem 283:18947-56. 2008
    ..Thus, EMILIN1 gC1q-alpha4beta1 represents a unique ligand/receptor system, with a requirement for a 3-fold arrangement of the interaction site...
  21. ncbi Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain
    Javier Redondo-Muñoz
    Centro de Investigaciones Biologicas, Madrid, Spain
    Cancer Cell 17:160-72. 2010
    ..Our results establish that MMP/receptor binding induces intracellular survival signals and highlight the role of (pro)MMP-9 in B-CLL pathogenesis...
  22. pmc Integrin alpha4beta1 signaling is required for lymphangiogenesis and tumor metastasis
    Barbara Garmy-Susini
    Department of Pathology, Moores Cancer Center, University of California San Diego, La Jolla, California 92093 0819, USA
    Cancer Res 70:3042-51. 2010
    ..We show here that the fibronectin-binding integrin alpha4beta1 and its ligand fibronectin are novel functional markers of proliferative lymphatic endothelium...
  23. ncbi Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine
    Maria Teresa de la Fuente
    Departamento de Inmunologia, Centro de Investigaciones Biologicas, CSIC, Velazquez 144, 28006 Madrid, Spain
    J Leukoc Biol 71:495-502. 2002
    ..These results indicate that Bcl-xL is involved in the survival signals induced by alpha4beta1 ligation and may contribute to the progressive drug resistance observed in B-CLL...
  24. ncbi Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis
    M Soilu-Hanninen
    Department of Virology, University of Turku, Finland
    J Neuroimmunol 72:95-105. 1997
    ..This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis...
  25. ncbi Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons
    Sherry T Hikita
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    Mol Cell Neurosci 23:427-39. 2003
    The integrin alpha4beta1 fulfills important roles in inflammation and hematopoesis, but its functions in neurons are not well understood...
  26. ncbi Alpha4beta1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells
    Javier Redondo-Muñoz
    Departamento de Fisiopatología Celular y Molecular, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain
    Blood 112:169-78. 2008
    ..Thus, we have identified alpha4beta1 and CD44v as a novel proMMP-9 cell surface docking complex and show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest...
  27. pmc Crystal structure of a heparin- and integrin-binding segment of human fibronectin
    A Sharma
    Laboratory of Molecular Biophysics, University of Oxford, Rex Richardson Building, South Parks Road, Oxford, OX1 3QU, UK
    EMBO J 18:1468-79. 1999
    ..The IDAPS motif implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering the critical Asp184 inaccessible to integrin...
  28. ncbi Integrin alpha4beta1 function is required for cell survival in developing retina
    Sergiu T Leu
    Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    Dev Biol 276:416-30. 2004
    ..We conclude that the integrin alpha4beta1 is important for survival of developing retinal neurons, including RGCs.
  29. pmc Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1
    David García-Bernal
    Department of Immunology, Centro de Investigaciones Biologicas, CSIC, 28006 Madrid, Spain
    Mol Biol Cell 16:3223-35. 2005
    The chemokine CXCL12 promotes T lymphocyte adhesion mediated by the integrin alpha4beta1. CXCL12 activates the GTPase Rac, as well as Vav1, a guanine-nucleotide exchange factor for Rac, concomitant with up-regulation of alpha4beta1-..
  30. ncbi Identification of a combinatorial epitope expressed by the integrin alpha 4 beta 1 heterodimer involved in the regulation of cell adhesion
    J L Bednarczyk
    Department of Immunology, University of Texas M D Anderson Cancer Center, Houston 77030
    J Biol Chem 269:8348-54. 1994
    ..Therefore, mAb 19H8 defined a novel regulatory epitope expressed by the integrin alpha 4 beta 1...
  31. ncbi Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin α-4-β-1 (VLA-4) with natalizumab can overcome this resistance
    Marek Mraz
    Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Br J Haematol 155:53-64. 2011
    ..These pre-clinical findings suggest that the addition of stromal adhesion-disruptive drugs to rituximab-containing therapy could improve treatment efficacy...
  32. pmc Dual functions of [alpha]4[beta]1 integrin in epicardial development: initial migration and long-term attachment
    Jennifer K Sengbusch
    Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Cell Biol 157:873-82. 2002
    ..T., H. Rayburn, and R.O. Hynes. 1995. Development. 121:549-560)...
  33. pmc Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells
    Gabriele Brachtl
    Laboratory for Immunological and Molecular Cancer Research, Third Medical Department With Hematology, Oncology, Hemostaseology, Infectiology and Rheumatology, Private Medical University Hospital, Salzburg, Austria
    PLoS ONE 6:e23758. 2011
    ..We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-stromal cell interactions...
  34. pmc Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity
    Martina Bauer
    Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Proc Natl Acad Sci U S A 106:1920-5. 2009
    ..Collectively, these results suggest that the primary action of natalizumab is interference with T cell extravasation via inhibition of alpha(4)beta(1) integrins...
  35. ncbi Alpha 4 beta 1 integrin-dependent cell adhesion is regulated by a low affinity receptor pool that is conformationally responsive to ligand
    T A Yednock
    Athena Neurosciences, Inc, South San Francisco, California 94080, USA
    J Biol Chem 270:28740-50. 1995
    ..These studies provide insight into how cells maintain different constitutive levels of alpha 4 beta 1 integrin activity, and how the activity of beta 1 integrin can be modulated by activators of cell adhesion...
  36. ncbi The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion
    Kim M T de Bruyn
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Universiteitsweg 100, P O Box 85060, 3508 AB Utrecht, The Netherlands
    J Biol Chem 277:29468-76. 2002
    ..We suggest that Rap1 determines the functional availability of integrins for productive binding to integrin ligands...
  37. ncbi Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic progenitor cells
    A Hidalgo
    , Department of Immunology, Madrid, Spain
    Exp Hematol 29:345-55. 2001
    ..Modulation of VLA-4-mediated CD34(hi) BM cell adhesion by SDF-1alpha could play a key role in their migration within and to the BM and therefore influence their proliferation and differentiation...
  38. ncbi Talin-1 and kindlin-3 regulate alpha4beta1 integrin-mediated adhesion stabilization, but not G protein-coupled receptor-induced affinity upregulation
    Sharon J Hyduk
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada
    J Immunol 187:4360-8. 2011
    ..Talin-1 contributed to α(4)β(1)-dependent chemotaxis, suggesting that it participates in a later stage of the leukocyte adhesion cascade when the leukocyte cytoskeleton undergoes dramatic rearrangement...
  39. ncbi Phospholipase C, calcium, and calmodulin are critical for alpha4beta1 integrin affinity up-regulation and monocyte arrest triggered by chemoattractants
    Sharon J Hyduk
    Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada
    Blood 109:176-84. 2007
    ..A critical role for PLC and calmodulin was also established for leukocyte arrest and adhesion strengthening...
  40. ncbi CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1 integrin for chemokine-induced motility on and through endothelium
    Kathleen J Till
    Department of Haematology, University of Liverpool, United Kingdom
    Blood 105:4813-9. 2005
    ..Given the importance of cell motility for tissue invasion, the present results provide a rationale for a trial of VEGF and alpha(4) blockade in patients with CLL who have tissue disease...
  41. pmc The pathophysiologic role of alpha 4 integrins in vivo
    R R Lobb
    Biogen, Inc, Cambridge, Massachusetts 02142
    J Clin Invest 94:1722-8. 1994
  42. pmc Integrin alpha4beta1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation
    Barbara Garmy-Susini
    John and Rebecca Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, California 92093 0912, USA
    J Clin Invest 115:1542-51. 2005
    ..Here we show that integrin alpha4beta1 (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interaction ..
  43. pmc Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain
    Ronen Alon
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Cell Biol 171:1073-84. 2005
    ....
  44. pmc Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development
    Shawdee Eshghi
    Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 177:871-80. 2007
    ....
  45. pmc Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion
    Marlena Duchniewicz
    Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D 14195 Berlin, Germany
    Mol Cell Biol 26:643-53. 2006
    ..Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins...
  46. ncbi Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases
    Helena Yusuf-Makagiansar
    Department of Pharmaceutical Chemistry, The University of Kansas, Simons Research Laboratory, 2095 Constant Avenue, Lawrence, Kansas 66047, USA
    Med Res Rev 22:146-67. 2002
    ..Finally, understanding the mechanism of LFA-1 and VLA-4 binding to their ligands has become a fundamental basis in developing therapeutic agents for inflammation and autoimmune diseases...
  47. ncbi Combinatorial chemistry identifies high-affinity peptidomimetics against alpha4beta1 integrin for in vivo tumor imaging
    Li Peng
    Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Cancer Center, University of California, Davis, 4501 X Street, Sacramento, California 95817, USA
    Nat Chem Biol 2:381-9. 2006
    ..Thus, LLP2A provides an important tool for noninvasive monitoring of alpha4beta1 expression and activity during tumor progression, and it shows great potential as an imaging and therapeutic agent for alpha4beta1-positive tumors...
  48. pmc BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells
    Pablo Ramirez
    Divisions of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 114:1340-3. 2009
    ..These data provide evidence for the utility of small molecule inhibitors of VLA-4 either alone or in combination with G-CSF or AMD3100 for mobilization of hematopoietic stem and progenitor cells...
  49. pmc Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/l-selectin, and lymphocyte function-associated antigen-1 adhesion pathways
    A Mikulowska Mennis
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 5324, USA
    Am J Pathol 159:671-81. 2001
    ..These adhesion molecules offer potential therapeutic targets to block the development of lacrimal gland inflammation and destruction...
  50. ncbi Natalizumab effects on immune cell responses in multiple sclerosis
    Masaaki Niino
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada
    Ann Neurol 59:748-54. 2006
    ..Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients...
  51. pmc TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner
    Inbal Binsky
    Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Immunol 184:4761-9. 2010
    ..These results could form the basis of novel therapeutic strategies aimed at blocking homing of CLL cells in their return to the BM and attenuating their survival...
  52. pmc Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1
    Young Min Hyun
    Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA
    J Immunol 183:359-69. 2009
    ..These data suggest that a subpopulation of activated VLA-4 is mainly localized to the leading edge of polarized human T cells and is critical for T cell migration on VCAM-1...
  53. ncbi Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1
    F Sanz-Rodriguez
    Department of Immunology, Centro de Investigaciones Biologicas, Madrid, Spain
    Blood 97:346-51. 2001
    ..Modulation of VLA-4-dependent myeloma cell adhesion by SDF-1alpha could contribute to the trafficking and localization of these cells in the BM microenvironment...
  54. pmc An alpha4beta1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice
    Nicholas J Kenyon
    Pulmonary and Critical Care Medicine, Genome and Biomedical Sciences Facility, Davis, CA 95616, United States
    Eur J Pharmacol 603:138-46. 2009
    ..Specifically engineered, PEGylated (PEG) formulations of this antagonist further reduce the airway inflammatory response to ovalbumin, presumably by improving the circulating half-life of the drug...
  55. ncbi Circulating B-cell chronic lymphocytic leukemia cells display impaired migration to lymph nodes and bone marrow
    Tanja Nicole Hartmann
    Laboratory for Immunological and Molecular Cancer Research, Third Medical Department, Salzburg University Hospital, Salzburg, Austria
    Cancer Res 69:3121-30. 2009
    ..Integrin blocking could thus be an efficient strategy to prevent circulating CLL cells from reaching prosurvival niches in LNs and BM but not in spleen...
  56. ncbi DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1
    David García-Bernal
    Department of Immunology, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain
    J Immunol 177:5215-25. 2006
    ....
  57. pmc B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1
    Yolanda R Carrasco
    Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London, UK
    EMBO J 25:889-99. 2006
    ..These results show that the VLA-4/VCAM-1 interaction during membrane antigen recognition enhances B-cell activation and this function appears to be independent of its final peripheral localization at the IS...
  58. pmc Sustained activation of cell adhesion is a differentially regulated process in B lymphopoiesis
    Aleksandra M Glodek
    Joint Program in Transfusion Medicine, Harvard Medical School, Children s Hospital Boston, Boston, MA 02115, USA
    J Exp Med 197:461-73. 2003
    ..These results provide a developmental cell stage-specific mechanism by which chemokines orchestrate hematopoiesis through sustained rather than transient activation of adhesion and cell survival pathways...
  59. pmc Galphas-coupled receptor signaling actively down-regulates alpha4beta1-integrin affinity: a possible mechanism for cell de-adhesion
    Alexandre Chigaev
    Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
    BMC Immunol 9:26. 2008
    ..Affinity and extension of VLA-4 are both rapidly up-regulated by inside-out signaling through several Galphai-coupled GPCRs. The goal of the current report was to study the effect of Galphas-coupled GPCRs upon integrin activation...
  60. ncbi Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism
    Stefano Pluchino
    Neuroimmunology Unit DIBIT, Vita Salute University, San Raffaele Hospital, Via Olgettina 58, 20132 Milan, Italy
    Nature 436:266-71. 2005
    ..These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection...
  61. pmc Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration
    Lawrence E Goldfinger
    Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, VB 2 La Jolla, CA 92037, USA
    J Cell Biol 162:731-41. 2003
    ..These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding...
  62. ncbi Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin
    V P Yakubenko
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute of The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Exp Cell Res 260:73-84. 2000
    ....
  63. ncbi VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells
    R A Oostendorp
    GSF Forschungszentrum für Umwelt und Gesundheit, Institut für Experimentelle Hämatologie, Munchen, Germany
    Leuk Lymphoma 24:423-35. 1997
    ..Moreover, these insights may explain how defects in adhesive behavior of leukemic HPC through VLA-4 contribute to their dysregulated growth and provide a rationale for therapeutically correcting those defects...
  64. ncbi Engagement of integrin alpha4beta1 enhances thrombopoietin-induced megakaryopoiesis
    Norma E Fox
    Department of Medicine, University of California San Diego, 92103 8811, USA
    Exp Hematol 33:94-9. 2005
    ..Moreover, a number of other hematopoietic cell types, including stem cells and erythroid progenitors, have been shown to engage and be affected by integrin ligands...
  65. ncbi Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos
    Alison Grazioli
    Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Biol 293:165-77. 2006
    ....
  66. pmc Sustained alterations in biodistribution of stem/progenitor cells in Tie2Cre+ alpha4(f/f) mice are hematopoietic cell autonomous
    Gregory V Priestley
    Division of Hematology, Department of Medicine, Box 357710, Seattle, WA 98195, USA
    Blood 109:109-11. 2007
    ....
  67. pmc Association between α4 integrin cytoplasmic tail and non-muscle myosin IIA regulates cell migration
    Leslie A Rivera Rosado
    Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Cell Sci 124:483-92. 2011
    ..These results provide a new mechanism for linking integrins to the actomyosin cytoskeleton and for regulating cell migration by integrins and non-muscle myosin II...
  68. ncbi Immobilized stromal cell-derived factor-1alpha triggers rapid VLA-4 affinity increases to stabilize lymphocyte tethers on VCAM-1 and subsequently initiate firm adhesion
    Jeffrey A DiVietro
    Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
    J Immunol 178:3903-11. 2007
    ..Chemokine activation of PBL firm adhesion on VCAM-1 depended on induction of high-affinity VLA-4 rather than recruitment of a pre-existing pool of high-affinity VLA-4 as previously thought...
  69. pmc alpha4 beta1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation
    Dustin A Dikeman
    Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Am J Physiol Cell Physiol 295:C151-9. 2008
    ..These findings provide a new insight into the mechanism by which integrins regulate directionally persistent cell migration...
  70. ncbi LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds
    Tatsuo Kinashi
    Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel
    Blood 103:1033-6. 2004
    ..This is a first report of an inherited Rap1 activation defect associated with a pathologic disorder in leukocyte integrin function, we herein term it "LAD-III."..
  71. pmc Dual functionality of the anti-beta1 integrin antibody, 12G10, exemplifies agonistic signalling from the ligand binding pocket of integrin adhesion receptors
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    J Biol Chem 280:10234-43. 2005
    ..Specifically, addition of 12G10 mAb to cells adhering via integrin alpha4beta1 was found to trigger disruption of the actin cytoskeleton and prevent cell attachment and spreading, ..
  72. ncbi Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of alpha 4 beta 1 and alpha 5 beta 1 integrins
    M Ramirez
    Unidad de Biología Molecular y Celular y Terapia Génica, CIEMAT, Madrid, Spain
    Br J Haematol 115:213-21. 2001
    ..However, in vivo, these effects induced an almost complete abrogation of the homing and repopulating ability of CD34(+) UCB cells...
  73. pmc Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma
    Allison L Zwingenberger
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    Vet Immunol Immunopathol 145:298-304. 2012
    ..In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics...
  74. ncbi Identification of 4-[1-[3-chloro-4-[N'-(5-fluoro-2-methylphenyl)ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]benzoic acid as a potent, orally active VLA-4 antagonist
    Fumihito Muro
    Medicinal Chemistry Research Laboratories II, Daiichi Sankyo Co, Ltd, 1 16 13, Kitakasai, Edogawa ku, Tokyo 134 8630, Japan
    Bioorg Med Chem 16:9991-10000. 2008
    ..Furthermore, this compound significantly blocked bronchial hyper-responsiveness in the model...
  75. ncbi Differential recruitment of alpha2beta1 and alpha4beta1 integrins to lipid rafts in Jurkat T lymphocytes exposed to collagen type IV and fibronectin
    Brian J Holleran
    Signal Transduction Laboratory, Graduate Program in Immunology, Clinical Research Center, University of Sherbrooke, 3001 12th Avenue North, Sherbrooke, Quebec, Canada J1H 5N4
    J Leukoc Biol 73:243-52. 2003
    ..The differential distributions of the alpha(2)beta(1) and alpha(4)beta(1) integrins in DRM may provide one additional step in the regulation of outside-in signaling involving these integrins...
  76. ncbi Potent in vivo suppression of inflammation by selectively targeting the high affinity conformation of integrin α4β1
    Peter Vanderslice
    Department of Drug Discovery, Biological Sciences, Encysive Pharmaceuticals, Inc, Houston, TX, USA
    Biochem Biophys Res Commun 400:619-24. 2010
    ....
  77. ncbi Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-1alpha and MIP-1beta production
    Masahiro Abe
    Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, 3 18 15 Kuramoto cho, Tokushima 770 8503, Japan
    J Bone Miner Metab 27:16-23. 2009
    ....
  78. ncbi Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice
    Laurence Pirson
    Center for Cellular and Molecular Therapy, University of Liege, Belgium
    Stem Cells 24:1814-21. 2006
    ..In summary, our results suggest that, despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib does not interfere with hematopoietic stem cell engraftment...
  79. ncbi Expression and function of integrin alpha4beta1 and vascular cell adhesion molecule-1 (VCAM-1) during sympathetic innervation of the heart
    Kevin L Wingerd
    Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    Dev Dyn 231:359-69. 2004
    The interaction between the integrin alpha4beta1 receptor on superior cervical ganglion (SCG) neurons and vascular cell adhesion molecule-1 (VCAM-1) in cardiac tissue has been implicated in proper development of the sympathetic ..
  80. ncbi Integrin alpha4beta1 involvement in stromal cell-derived factor-1alpha-promoted myeloma cell transendothelial migration and adhesion: role of cAMP and the actin cytoskeleton in adhesion
    Marisa Parmo-Cabañas
    Centro de Investigaciones Biologicas, Department of Immunology, Madrid, Spain
    Exp Cell Res 294:571-80. 2004
    ..Myeloma cells express the SDF-1alpha receptor CXCR4, as well as the integrin alpha4beta1, which mediates their attachment to BM stroma...
  81. ncbi Adhesion molecule mechanisms mediating monocyte migration through synovial fibroblast and endothelium barriers: role for CD11/CD18, very late antigen-4 (CD49d/CD29), very late antigen-5 (CD49e/CD29), and vascular cell adhesion molecule-1 (CD106)
    X Z Shang
    Department of Pediatrics, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
    J Immunol 160:467-74. 1998
    ..In addition to VCAM-1, other ligand(s) on HSF are also involved in the VLA-4-mediated migration...
  82. ncbi Quantitative expression of adhesion molecules on granulocyte colony-stimulating factor-mobilized peripheral blood, bone marrow, and cord blood CD34+ cells
    C Gigant
    , LEMTA UMR CNRS 7563, , , France
    J Hematother Stem Cell Res 10:807-14. 2001
    ..Finally, the quantitative expression of the main receptors on CD34(+) cells explained cellular functions during the different steps of hematopoietic stem cells transplantation...
  83. ncbi Endothelial expression of VCAM-1 in experimental crescentic nephritis and effect of antibodies to very late antigen-4 or VCAM-1 on glomerular injury
    A R Allen
    Renal Section, Division of Medicine, British Heart Foundation Cardiovascular Medicine Unit, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
    J Immunol 162:5519-27. 1999
    ..However, VLA-4 is an important mediator of glomerular injury, operating after transendothelial leukocyte migration, and presumably binding to alternate ligands within the kidney...
  84. ncbi Modulation of integrin alpha4beta1 (VLA-4) in dry eye disease
    Tatiana Ecoiffier
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA
    Arch Ophthalmol 126:1695-9. 2008
    ..To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti-VLA-4 sm) in a mouse model of dry eye disease...
  85. ncbi Role of alpha4beta1 integrins in chemokine-induced monocyte arrest under conditions of shear stress
    Sharon J Hyduk
    Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, Ontario, Canada
    Microcirculation 16:17-30. 2009
    ....
  86. pmc Relationship between molecular and cellular dissociation rates for VLA-4/VCAM-1 interaction in the absence of shear stress
    Gordon Zwartz
    Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    Biophys J 86:1243-52. 2004
    ..5 +/- 0.7. This suggests that a few bonds were needed to form cellular aggregates and that increased aggregation was related to integrin affinity changes and not due to clustering or increased bond numbers...
  87. ncbi Real time analysis of the affinity regulation of alpha 4-integrin. The physiologically activated receptor is intermediate in affinity between resting and Mn(2+) or antibody activation
    A Chigaev
    Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    J Biol Chem 276:48670-8. 2001
    ..It appears that the physiologically active state of the alpha(4)-integrin, determined by inside-out signaling, has similar affinity in several cell types...
  88. pmc alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism
    Karen A Pinco
    Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Biol Cell 13:3203-17. 2002
    ....
  89. ncbi Effect of divalent cations on the affinity and selectivity of alpha4 integrins towards the integrin ligands vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1: Ca2+ activation of integrin alpha4beta1 confers a distinct ligand
    Eric S Day
    Biogen Inc, Cambridge, MA 02142, USA
    Cell Commun Adhes 9:205-19. 2002
    ..However, the Ca2+-activated state of alpha4beta1 is distinct from that achieved by Mn2+ and Mg2+, possessing increased selectivity for binding to VCAM-1 versus MAdCAM-1...
  90. ncbi Regulation of cell adhesion by affinity and conformational unbending of alpha4beta1 integrin
    Alexandre Chigaev
    Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
    J Immunol 178:6828-39. 2007
    ....
  91. ncbi Immune surveillance in multiple sclerosis patients treated with natalizumab
    Olaf Stuve
    Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, USA
    Ann Neurol 59:743-7. 2006
    ....
  92. pmc Real-time analysis of conformation-sensitive antibody binding provides new insights into integrin conformational regulation
    Alexandre Chigaev
    Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    J Biol Chem 284:14337-46. 2009
    ..Our data suggest that VLA-4 integrin hybrid domain movement does not depend on the affinity state of the ligand binding pocket...
  93. pmc Discovery of very late antigen-4 (VLA-4, alpha4beta1 integrin) allosteric antagonists
    Alexandre Chigaev
    Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    J Biol Chem 286:5455-63. 2011
    ..Because all the identified compounds are structurally related, previously used, or currently marketed drugs, this result opens a range of therapeutic possibilities for VLA-4-related pathologies...
  94. ncbi Integrin-associated protein (CD47/IAP) contributes to T cell arrest on inflammatory vascular endothelium under flow
    M Ticchioni
    Unité INSERM U343 et Laboratoire d Immunologie, 06202 Nice Cedex 3, France
    FASEB J 15:341-50. 2001
    ..Blocking experiments show that both are involved. Overall, CD47 participates in the constitutive arrest of T lymphocytes on inflamed vascular endothelium by up-regulating alpha 4beta1 integrins...
  95. ncbi EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall
    Paola Spessotto
    Divisione di Oncologia Sperimentale 2, CRO IRCCS, 33081 Aviano, Italy
    J Cell Sci 119:4574-84. 2006
    ..Finally, membrane type I-matrix metalloproteinase (MT1-MMP) and MMP-2 were upregulated in co-cultures of trophoblast cells and stromal cells, suggesting a contributing role in the haptotactic process towards EMILIN1...
  96. ncbi IFN-alpha subtypes differentially affect human T cell motility
    Graham R Foster
    Hepatobiliary Group, Department of Gastroenterology, Queen Mary s School of Medicine and Dentistry at Barts and The Royal London Hospital, United Kingdom
    J Immunol 173:1663-70. 2004
    ..These observations are consistent with the possibility that subtype-specific intracellular signaling pathways are activated by type I IFNs in T lymphocytes...
  97. ncbi EWI-2 modulates lymphocyte integrin alpha4beta1 functions
    Tatiana V Kolesnikova
    Dana Farber Cancer Institute, Brigham and Women s Hospital, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Blood 103:3013-9. 2004
    The most prominent cell-surface integrin alpha4beta1 partner, a 70-kDa protein, was isolated from MOLT-4 T leukemia cells, using anti-alpha4beta1 integrin antibody-coated beads...
  98. pmc Integrin alpha4beta1 regulates migration across basement membranes by lung fibroblasts: a role for phosphatase and tensin homologue deleted on chromosome 10
    Eric S White
    Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, 6301 MSRB III 0642, 1150 West Medical Center Drive, Ann Arbor, MI 48109 0642, USA
    Am J Respir Crit Care Med 168:436-42. 2003
    ..Furthermore, this study implicates a loss of PTEN function in the pathophysiology of idiopathic pulmonary fibrosis...
  99. pmc Integrin alpha4beta1 promotes focal adhesion kinase-independent cell motility via alpha4 cytoplasmic domain-specific activation of c-Src
    Datsun A Hsia
    The Scripps Research Institute, Department of Immunology, IMM21, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell Biol 25:9700-12. 2005
    ....
  100. ncbi A region of the integrin VLA alpha 4 subunit involved in homotypic cell aggregation and in fibronectin but not vascular cell adhesion molecule-1 binding
    M Munoz
    Centro de Investigaciones Biologicas, Departamento de Inmunologia, Madrid, Spain
    J Biol Chem 271:2696-702. 1996
    ..Altogether, these results indicate that alpha 4 residues Arg89 and Asp90 are included in a region involved in homotypic cell aggregation, as well as in adhesion to FN-40, but not to VCAM-1...
  101. ncbi VLA-4 integrin cross-linking on human monocytic THP-1 cells induces tissue factor expression by a mechanism involving mitogen-activated protein kinase
    I D McGilvray
    Departments of Surgery, Toronto Hospital General Division and the University of Toronto, Toronto, Ontario M5G 2C4, Canada
    J Biol Chem 272:10287-94. 1997
    ..These studies point to the involvement of the MAP kinase pathway in the activation of monocytic cells during transmigration to inflammatory sites...

Research Grants63

  1. PATHOPHYSIOLOGY OF THE ENDOTHELIUM
    Francis W Luscinskas; Fiscal Year: 2013
    ..g., heart attacks and strokes), as well as other organs and tissues of the body. These mechanistic insights may help identify novel therapeutic targets for the treatment of a broad spectrum of inflammatory diseases. ..
  2. Molecular Mechanism of Immune Therapy for Bone Marrow Failures
    Pearlie K Epling-Burnette; Fiscal Year: 2013
    ..Additionally, the efficacy of pharmacological inhibitors to block homing to the bone marrow will be tested to provide critical pre-clinical data for application to clinical studies in patients in the future. ..
  3. Molecular Imaging of Metastatic Potential in SCCHN by Targeting VLA-4 and CXCR4
    Carolyn J Anderson; Fiscal Year: 2013
    ....
  4. RECEPTOR TARGETED MOLECULAR IMAGING OF MULTIPLE MYELOMA
    Monica Shokeen; Fiscal Year: 2013
    ..These aims will help in the accurate assessment of early stage disease and treatment response by sensitive and specific VLA-4 targeted PET imaging. ..
  5. T Cell Memory in Organ Transplantation
    Fadi G Lakkis; Fiscal Year: 2010
    ..Congenic markers will be used to track adoptively transferred CD8 memory T cells. Gene knockout mice and monoclonal antibodies will be used to examine the roles of chemokine receptors and adhesion molecules. ..
  6. Novel Immunotherapy of Glioma using miR-17-92 Transfected T Cells
    Hideho Okada; Fiscal Year: 2013
    ..The currently proposed preclinical study will evaluate an entirely novel immunotherapy approach with engineering of microRNAs in anti-tumor T cells, which we hope to translate into clinical trials in near future. ..
  7. TARGETING AML-STROMAL INTERACTIONS
    John F DiPersio; Fiscal Year: 2013
    ..We hypothesize that pharmacologic interruption of the tethers that bind AML blasts to the bone marrow will sensitize these cells to chemotherapy and improve remission rates and long term disease free survival. ..
  8. CXCR4 regulation of tumor progression in Multiple Myeloma
    Irene M Ghobrial; Fiscal Year: 2012
    ..Targeting this process by mobilizing myeloma cells out of the marrow will lead to a higher sensitivity to killing of the cells with cytotoxic agents. ..
  9. Mechanisms of Integrin-Mediated Costimulation in T Cells
    Stephen C Bunnell; Fiscal Year: 2013
    ..In this manner, we expect to gain useful insights into the underlying causes of common medical conditions, including asthma, multiple sclerosis, diabetes, inflammatory bowel disease, and atherosclerosis. ..
  10. Translational applications of Progressive Multifocal Leukoencephalopathy studies
    Igor J Koralnik; Fiscal Year: 2012
    ..These studies will certainly appeal to young individuals interested to launch their careers in the fields of Neurology, Neurolmaging, Infectious Diseases, Virology, Immunology, Hematology, Nephrology and Pathology. ..
  11. Efficient Targeting of Therapeutic Cells in Stroke and EAE
    Piotr Walczak; Fiscal Year: 2013
    ..Upon successful completion of our studies, this new targeting approach could significantly improve the efficacy of cell-based therapy with applications in many areas of medicine. ..
  12. Targeting Agents for Human and Canine Lymphoma
    Kit Lam; Fiscal Year: 2009
    ..abstract_text> ..
  13. TARGETING REGULATORS OF APOPTOSIS IN AML
    MICHAEL W ANDREEFF; Fiscal Year: 2011
    ..If successful, these studies will provide rationale for greatly improved therapies for AML that target both, the leukemic cells and their microenvironment. ..
  14. Prognostic and Functional Significance of Adhesion Molecules in Pediatric AML
    ROLAND BRUNO WALTER; Fiscal Year: 2013
    ....
  15. Targeting CD44 in the bone marrow microenvironment of MM
    Rajesh R Nair; Fiscal Year: 2012
    ..To this end this proposal will determine whether the cyclized peptide referred to as cHYD1 is an attractive strategy to combine with standard therapy for the treatment of myeloma. ..
  16. The role of beta1 integrin in modulating gut-homing alpha4beta7 on T cells
    CHRISTOPHER CHARLES DENUCCI; Fiscal Year: 2010
    ..Following T cell activation, the extra-intestinal homing integrin alpha4beta1 and the gut-homing integrin alpha4beta7 are involved in directing the targeted migration of T cells...
  17. Increasing the efficacy of MTI-101 in MM using Ab conjugation strategies
    Christoph Rader; Fiscal Year: 2013
    ....
  18. THE CHEMOKINE RECEPTOR CXCR-2 IN ATHEROSCLEROSIS
    William Boisvert; Fiscal Year: 2002
    ..e. in vivo correlation studies between CXCR2 expression and PCNA, oxidized LDL antigens, and scavenger receptor expression). ..
  19. Migration of polyomavirus JC across the blood-brain-barrier
    Vivek Nerurkar; Fiscal Year: 2009
    ....
  20. Hematopoietic Stem Cell Therapy for Myocardial Regeneration
    Roberto Bolli; Fiscal Year: 2007
    ..The results may eventually lead to the development of novel therapeutic strategies in patients with ischemic heart disease. ..
  21. MOLECULAR MECHANISMS IN METASTASIS--ROLE OF FIBRONECTIN
    LEO FURCHT; Fiscal Year: 2001
    ..The overall goal in these studies is to define the molecular mechanisms that regulate CSPG/alpha4beta1 integrin interactions and to evaluate their importance in tumor cell adhesion, invasion and metastasis. ..
  22. MOUSE MODEL OF EOSINOPHIL MEDIATED SKIN PATHOLOGY
    James Lee; Fiscal Year: 1999
    ....
  23. NEUTROPHIL SEQUESTRATION AND EMIGRATION IN THE LUNG
    CLAIRE DOERSCHUK; Fiscal Year: 2001
    ..These studies will help to understand biomechanical and adhesive events and their interactions during inflammation and will examine the therapeutic potential of altering biomechanical events to modulate the inflammatory response. ..
  24. Substrata Interactions of Normal and Leukemic Hematopoietic Stem Cells
    Jane Liesveld; Fiscal Year: 2009
    ..They also have implication for understanding of survival and proliferation of normal stem cells which would have impact on stem cell transplantation and implantation therapies. ..
  25. Poly (amino acid) as an Integrin Targeted Drug Carrier
    Xiaoling Li; Fiscal Year: 2005
    ..of the Pacific, a primarily baccalaureate training institution. ..
  26. T CELL ADHESION MOLECULES IN MURINE LUPUS PNEUMONITIS
    Jeffrey Curtis; Fiscal Year: 2002
    ..Our long-term goal is to develop effective therapies to treat established SLE based on anti-adhesive strategies. ..
  27. Optimizing Osteotropism of Human Mesenchymal Stem Cells
    Robert Sackstein; Fiscal Year: 2010
    ....
  28. LEUKOCYTE ADHESION IN ALLERGIC INFLAMMATION
    P Sriramarao; Fiscal Year: 1999
    ..These proposed studies are intended to give a better understanding of molecular mechanisms mediating cell adhesion and provide a basis for examining therapeutic strategies for the treatment of allergic inflammation. ..
  29. ADHESION MOLECULES IN SMOOTH MUSCLE ACTIVATION & GROWTH
    AILI LAZAAR; Fiscal Year: 2003
    ..Understanding the mechanisms by which CAMs transduce signals that could induce myocyte activation may provide insight in new therapeutic measures to prevent airway inflammation and bronchial hyperreactivity. ..
  30. Regulation of Integrin Alpha4 Betal
    MARK HOWARD GINSBERG; Fiscal Year: 2010
    ..These fundamental studies will provide new insight into the regulation of inflammation and will test and advance paradigms that could lead to novel therapies for Rheumatic Diseases. ..
  31. VLA-4 And VCAM-1 in Advanced Atherosclerosis
    John Harlan; Fiscal Year: 2005
    ..To complement the VLA- 4 studies, we will also examine the role of VCAM-1 in lesion initiation/progression in a model of conditional knockout of endothelial VCAM-1 (Aim 3). ..
  32. Cytoplasmic Regulation of a4b1 Avidity under Flow
    Mark Ginsberg; Fiscal Year: 2005
    ..This research will be done in Israel at the Weizmann Institute of Science in collaboration with Dr. Mark Ginsberg as an extension of NIH grants AR 27214 and HL 31950. ..
  33. Treatment of Multiple Sclerosis
    Anthony Reder; Fiscal Year: 2009
    ..of Health Studies and its K30 program, and educate fellows in trial design, statistics, and all neurologic aspects of MS. ..
  34. HIV-Specific T-cells in cerebrospinal fluid (CSF)
    Barbara Shacklett; Fiscal Year: 2004
    ..We also hypothesize that there may be a correlation between intrathecal HIV viral load and T-cell recruitment to CSF, and that the presence of CTL in CSF may be predictive of neurological disease. ..
  35. VLA4 IN CTL MEDIATED ISLET ALLOGRAFT REJECTION
    Mark Stegall; Fiscal Year: 2001
    ..The approach may lead to novel forms of immune suppression that may benefit not only islet transplantation, but also other types of organ allografts. ..
  36. ROLE OF FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
    RICARDO FELDMAN; Fiscal Year: 2004
    ..This will have an impact on the rational design of therapies aimed at preventing the inappropriate activation of macrophages, a biomedical problem of paramount importance. ..
  37. PATHOPHYSIOLOGY OF RENAL TUBULAR CELLS
    Frank Lee; Fiscal Year: 2002
    ....
  38. ALCOHOL, IMMUNOSUPRESSION, AND PNEUMOCYSTIS CARINII
    JUDD SHELLITO; Fiscal Year: 1999
    ....
  39. VASO-OCCLUSIVE PROCESSES IN SICKLE CELL RETINOPATHY
    Gerard Lutty; Fiscal Year: 2006
    ..abstract_text> ..
  40. Bone and the Hematopoietic System
    Russell Taichman; Fiscal Year: 2004
    ..These investigations will ultimately lead to new strategies for the treatment of hematopoietic and osseous disorders. ..
  41. Leukocyte C2GIcNAcT-I in atherosclerosis
    Yuqing Huo; Fiscal Year: 2009
    ..These studies will have significant implications for the inhibition of leukocyte C2GlcNAcT-l in the prevention and treatment of atherosclerosis and its complications. ..
  42. B LINEAGE DEVELOPMENT OF HUMAN HEMATOPOIETIC PROGENITORS
    Daniel Ryan; Fiscal Year: 2000
    ....
  43. REG OF BETA 2 INTEGRIN ADHESION IN TL LYMPHOMA CELL
    LLOYD KLICKSTEIN; Fiscal Year: 1999
    ....
  44. HIV INFECTED ENDOTHELIUM AND NONHODGKINS LYMPHOMA
    Ashlee Moses; Fiscal Year: 2002
    ..Identification of these mechanisms may suggest therapeutic targets to prevent development of extranodal B cell neoplasms. ..
  45. ZEB AND ZFH1 AND MYOGENESIS
    Douglas Dean; Fiscal Year: 2003
    The specific aims during the last grant-period were to examine the roles of the integrin alpha4beta1 and its cell surface ligand VCAM-1 in muscle differentiation, and to determine how expression of the proteins are regulated in this ..
  46. INTEGRINS AND T CELL DEVELOPMENT AND FUNCTION
    EUGENE MARCANTONIO; Fiscal Year: 2002
    ..We specifically show that there is a reduction in the expression of an activation epitope in the integrin alpha4beta1. Our hypothesis is that this construct has decreased the activation of a number of integrin receptors, ..
  47. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    LESLIE RIVERA; Fiscal Year: 2006
    ..abstract_text> ..
  48. CARDIAC TRANSPLANT ATHEROSCLEROSIS
    Paul Russell; Fiscal Year: 2000
    ..The results derived from these studies are expected to suggest fruitful approaches to the control of the important process of transplant arteriopathy. ..
  49. ENDOTHELIUM--SIGNALING FROM MAST CELLS TO EOSINOPHILS
    David Broide; Fiscal Year: 2002
    ....
  50. Hyposialylation Regulates Alpha4Beta1 Integrin Binding to VCAM1
    ALENCIA WOODARD GRICE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  51. GLOBIN SWITCHING AND ERYTHROID DIFFERENTIATION
    Thalia Papayannopoulou; Fiscal Year: 2002
    ....
  52. BIOLOGICAL PROPERTIES AND REGULATION OF STEM CELLS
    Thalia Papayannopoulou; Fiscal Year: 2009
    ..We believe that the proposed studies will enhance our understanding and provide a more comprehensive picture of the influence of <x4 integrins on prenatal and postnatal hematopoiesis. ..
  53. PEPTIDE MEDIATED IMMUNOTHERAPY FOR AUTOIMMUNE DISEASE
    Lawrence Steinman; Fiscal Year: 2003
    ..This work with APL may be applicable not only to MS, but to other autoimmune diseases including juvenile diabetes, rheumatoid arthritis, and inflammatory bowel disease. ..
  54. Large Scale Images of Gene Transcription in MS and EAE
    Lawrence Steinman; Fiscal Year: 2004
    ..The discovery of the role of osteopontin, first identified in large scale profiles, exemplifies how this approach may help us to understand MS and to develop new therapies. ..
  55. IN VIVO TREATMENT OF EAE WITH ANTI I-A ANTIBODIES
    Lawrence Steinman; Fiscal Year: 2001
    ..Aim 5 is to assess the possibility of using DNA vaccination against TCR Vb for treatment of EAE. It is hoped that these studies will provide the basis for future clinical trials in MS patients. ..
  56. Nanoparticle delivery of antiangiogenic genes
    Gerard Lutty; Fiscal Year: 2003
    ..The goal of this proposal is to deliver genes for endogenous antiangiogenic agents to sites of ocular neovascularization. ..
  57. Acquisition of FACSVantage SE Flow Cytometer
    Yair Gazitt; Fiscal Year: 2004
    ..The new equipment will also widen the user's base, save sort time, reduce costs for users and will render sorting affordable to new users, especially in cases where low frequency (<1%) cell populations are sorted. ..
  58. NEUROSCIENCE OF HIV CONFERENCE
    Joseph Berger; Fiscal Year: 2002
    ..Dr. Brian Wigdahl, international co-chair of the ISNV, is a co-investigator on this grant. ..
  59. Growth factors and engineered stroma for hematopoietic stem csll (HSC) expansion
    Harvey F Lodish; Fiscal Year: 2010
    ..The ability to expand HSCs ex vivo would greatly enhance these clinical applications, in the case of gene therapy allowing selection of those HSCs that have integrated a transgene in a specific chromosomal location. ..
  60. ADAM Proteolytic and Adhesive Function in Cell Migration
    LANCE BRIDGES; Fiscal Year: 2006
    ..abstract_text> ..
  61. IMMUNOREGULATORY EFFECTS OF ESTROGEN IN EAE
    Halina Offner; Fiscal Year: 2010
    ..E2 in relapsing, chronic, and spontaneous models of EAE. These studies will clearly establish E2- and EE- dependent pathways of EAE protection and therapy that may have direct relevance for future clinical trials in MS patients. ..
  62. Novel Dendritic Cell Chemoattractant and Receptor
    Eugene Butcher; Fiscal Year: 2009
    ..abstract_text> ..