integrin alpha4

Summary

Summary: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.

Top Publications

  1. ncbi A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis
    Chris H Polman
    Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    N Engl J Med 354:899-910. 2006
  2. ncbi Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses
    S Liu
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 402:676-81. 1999
  3. pmc Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab
    Halvard Bonig
    Department of Medicine Hematology, University of Washington, Seattle, USA
    Blood 111:3439-41. 2008
  4. ncbi Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis
    B K Kleinschmidt-Demasters
    Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA
    N Engl J Med 353:369-74. 2005
  5. pmc Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing
    Linda M Scott
    Division of Hematology, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195 7710, USA
    Mol Cell Biol 23:9349-60. 2003
  6. pmc Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site
    Chloe C Feral
    Department of Medicine, University of California San Diego, La Jolla, California 92093 0726, USA
    J Clin Invest 116:715-23. 2006
  7. ncbi Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9
    Andrea G S Buggins
    Department of Haematological Medicine, King s College London, London, UK
    Br J Haematol 154:216-22. 2011
  8. pmc A small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation
    Christiane Kummer
    Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA
    J Biol Chem 285:9462-9. 2010
  9. ncbi Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding
    J Han
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 276:40903-9. 2001
  10. ncbi Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS
    Richard A Rudick
    Department of Neurology, Center for Multiple Sclerosis Treatment and Research, Cleveland, OH 44195, USA
    Expert Rev Neurother 4:571-80. 2004

Research Grants

  1. FIBRONECTIN REGULATION OF CARCINOMA APOPTOSIS
    Yvonne Kapila; Fiscal Year: 2009
  2. Role of alpha4-paxillin signaling in lymphangiogenesis
    CHRISTIE AVRAAMIDES; Fiscal Year: 2010
  3. MOLECULAR MECHANISMS IN METASTASIS--ROLE OF FIBRONECTIN
    LEO FURCHT; Fiscal Year: 2001
  4. Selectin Control of Leukocyte Adhesion in Shear
    Michael Lawrence; Fiscal Year: 2006
  5. A4B7 INTEGRIN IN INTESTINAL INFLAMMATION AND IMMUNITY
    Eugene Butcher; Fiscal Year: 1999
  6. Regulation of Integrin Alpha4 Betal
    MARK HOWARD GINSBERG; Fiscal Year: 2010
  7. VCAM 1 EXPRESSION IN ENDOTHELIAL CELLS
    Douglas Dean; Fiscal Year: 1999
  8. SPECIFIC INTEGRIN ALPHA 4 CYTOPLASMIC TAIL FUNCTIONS
    MARTIN HEMLER; Fiscal Year: 1999
  9. ZEB IN LEUKOCYTE DIFFERENTIATION AND FUNCTION
    Douglas Dean; Fiscal Year: 2002
  10. Vascular responses in transgenic sickle cell mice
    Beatrice Gee; Fiscal Year: 2007

Detail Information

Publications218 found, 100 shown here

  1. ncbi A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis
    Chris H Polman
    Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    N Engl J Med 354:899-910. 2006
    ..Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis...
  2. ncbi Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses
    S Liu
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 402:676-81. 1999
    ..Thus, the tight association of paxillin with the alpha4 tail leads to distinct biochemical and biological responses to integrin-mediated cell adhesion...
  3. pmc Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab
    Halvard Bonig
    Department of Medicine Hematology, University of Washington, Seattle, USA
    Blood 111:3439-41. 2008
    ..The blood of natalizumab-treated subjects also contained SCID-repopulating cells. The fate of these circulating HSPCs and their clinical relevance for MS patients remains to be determined...
  4. ncbi Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis
    B K Kleinschmidt-Demasters
    Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA
    N Engl J Med 353:369-74. 2005
    ..There was extensive tissue destruction and cavitation in the left frontoparietal area, large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes, which were positive for JC virus DNA on in situ hybridization...
  5. pmc Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing
    Linda M Scott
    Division of Hematology, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195 7710, USA
    Mol Cell Biol 23:9349-60. 2003
    ....
  6. pmc Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site
    Chloe C Feral
    Department of Medicine, University of California San Diego, La Jolla, California 92093 0726, USA
    J Clin Invest 116:715-23. 2006
    ..We conclude that interference with alpha4 integrin signaling can selectively impair mononuclear leukocyte recruitment to sites of inflammation while sparing vital functions of alpha4 integrins in development and hematopoiesis...
  7. ncbi Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9
    Andrea G S Buggins
    Department of Haematological Medicine, King s College London, London, UK
    Br J Haematol 154:216-22. 2011
    ..Our findings provide a molecular basis for the correlation between expression of these proteins and prognosis and, as the complex is not present in normal B-cells, suggest a novel leukaemia-specific therapeutic target...
  8. pmc A small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation
    Christiane Kummer
    Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA
    J Biol Chem 285:9462-9. 2010
    ....
  9. ncbi Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding
    J Han
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 276:40903-9. 2001
    ..Consequently, alpha4 phosphorylation is a biochemical mechanism to modulate paxillin binding to alpha4 integrins with consequent regulation of alpha4 integrin-dependent cellular functions...
  10. ncbi Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS
    Richard A Rudick
    Department of Neurology, Center for Multiple Sclerosis Treatment and Research, Cleveland, OH 44195, USA
    Expert Rev Neurother 4:571-80. 2004
    ..Natalizumab may be an important addition to the therapeutic armamentarium for multiple sclerosis...
  11. ncbi Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients
    Raija L P Lindberg
    Clinical Neuroimmunology Laboratory, Departments of Research and Neurology, University Hospital Basel, Switzerland
    J Neuroimmunol 194:153-64. 2008
    ..Understanding these different gene effects and their interrelationships will provide more insights into additional mechanisms of action of natalizumab and possibly allow better prediction of adverse events...
  12. ncbi Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development
    J T Yang
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Development 121:549-60. 1995
    ..These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation...
  13. ncbi Natalizumab dosage suspension: are we helping or hurting?
    Timothy W West
    Multiple Sclerosis Center, University of California at San Francisco, San Francisco, CA, USA
    Ann Neurol 68:395-9. 2010
    ..Some of these flares can be clinically severe, with a high number of contrast-enhanced lesions, suggesting a possible rebound of disease activity...
  14. ncbi Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice
    L Kwee
    Department of Biotechnology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110 1199, USA
    Development 121:489-503. 1995
    ..These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart...
  15. ncbi Galectin-3 functions as an adhesion molecule to support eosinophil rolling and adhesion under conditions of flow
    Savita P Rao
    Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA
    J Immunol 179:7800-7. 2007
    ..These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow...
  16. pmc EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation
    Carla Danussi
    Division of Experimental Oncology 2, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, National Cancer Institute, 33081 Aviano, Italy
    J Cell Biol 195:131-45. 2011
    ..In addition, EMILIN1 is identified as a novel ligand for keratinocyte α9β1 integrin, suggesting prospective roles for this receptor-ligand pair in skin homeostasis...
  17. ncbi Progressive multifocal leukoencephalopathy in a patient treated with natalizumab
    Annette Langer-Gould
    Department of Neurology, Stanford University School of Medicine, Stanford, Calif, USA
    N Engl J Med 353:375-81. 2005
    ..The patient was treated with systemic cytarabine, and two months later, his condition had improved...
  18. ncbi Natalizumab plus interferon beta-1a for relapsing multiple sclerosis
    Richard A Rudick
    Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    N Engl J Med 354:911-23. 2006
    ..Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies...
  19. ncbi Investigating the role of CD38 and functionally related molecular risk factors in the CLL NOD/SCID xenograft model
    Semra Aydin
    Department of Hematology, University of Duisburg Essen Medical School, Essen, Germany
    Eur J Haematol 87:10-9. 2011
    ..This model could be useful for evaluating the biological basis of CLL growth in the context of the hematopoietic microenvironment as well as preclinical testing of novel compounds...
  20. ncbi A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B-cell chronic lymphocytic leukemia
    Antonella Zucchetto
    Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I R C C S, Aviano PN, Italy
    J Cell Physiol 207:354-63. 2006
    ..The proposed immunophenotypic scoring system may be an additional useful tool in routine diagnostic/prognostic procedures for B-CLL...
  21. ncbi High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia
    Holger Nuckel
    Department of Haematology, University of Duisburg Essen, Germany
    Clin Immunol 131:472-80. 2009
    ..Collectively, our data confirm the prognostic significance supporting the idea to use CD49d as target molecules for therapeutic approaches in B-CLL...
  22. pmc NMR structure of integrin α4 cytosolic tail and its interactions with paxillin
    Geok Lin Chua
    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    PLoS ONE 8:e55184. 2013
    ..CTs of integrins are important in bidirectional signal transduction and they associate with a large number of intracellular proteins...
  23. ncbi The alpha4 subunit of integrin is important for neural crest cell migration
    S H Kil
    Division of Biology 139 74, California Institute of Technology, Pasadena, California, 91125, USA
    Dev Biol 202:29-42. 1998
    ..Using degenerate primers, we obtained a PCR fragment of the chick integrin alpha4 subunit that was subsequently used to clone the full-length subunit with a predicted amino acid sequence 60% ..
  24. ncbi CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function
    D Jing
    Department of Hematology and Oncology, University Hospital Dresden, Dresden, Germany
    Bone Marrow Transplant 45:1489-96. 2010
    ..Our data indicate that G-CSF and CD49d blockade mobilize different HSC subsets and suggest that both strategies may be differentially applied in specific cell therapy approaches...
  25. ncbi Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo
    A G Arroyo
    Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts 02139, USA
    Immunity 11:555-66. 1999
    ..In summary, alpha4 integrins are essential for normal development of all hematopoietic lineages in fetal liver, bone marrow, and spleen, likely by regulating the proliferation/differentiation balance of hematopoietic progenitors...
  26. ncbi Differential requirements for alpha4 integrins during fetal and adult hematopoiesis
    A G Arroyo
    Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA
    Cell 85:997-1008. 1996
    ..We also show that alpha4 integrins are essential for T cell homing to Peyer's patches, but not to other secondary lymphoid organs, including spleen, lymph nodes, and intestinal epithelium...
  27. 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
  28. 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
    ....
  29. pmc Complementary roles of retinoic acid and TGF-β1 in coordinated expression of mucosal integrins by T cells
    S G Kang
    Department of Comparative Pathobiology, The Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA
    Mucosal Immunol 4:66-82. 2011
    ..The retinoic acid-mediated regulation of α(4) integrins is required for specific migration of T cells in vitro and in vivo. These results provide central regulatory mechanisms for coordinated expression of the major mucosal integrins...
  30. ncbi Alpha4 integrins and the immune response
    David M Rose
    Division of Rheumatology, Allergy, and Immunology, Department of Medicine, The University of California, San Diego, California, USA
    Immunol Rev 186:118-24. 2002
    ..Furthermore, this protein-protein interaction may provide novel targets for the modulation of the immune response...
  31. ncbi Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia
    Valter Gattei
    Clinical and Experimental Onco Hematology Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico Aviano, Italy
    Blood 111:865-73. 2008
    ..95; P=.002) cases. These findings support the introduction of CD49d detection in routine prognostic assessment of CLL patients, and suggest both pathogenetic and therapeutic implications for CD49d expression in CLL...
  32. pmc Antibodies to CD44 and integrin alpha4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment
    S Brocke
    Neurological Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 1400, USA
    Proc Natl Acad Sci U S A 96:6896-901. 1999
    ..Activated T cell lines and clones expressed CD44 and integrin alpha4, but not L-selectin, and entered the CNS independent of their antigen specificity...
  33. 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...
  34. ncbi The role of the alpha4 integrin-paxillin interaction in regulating leukocyte trafficking
    David M Rose
    Department of Medicine, University of California VA Medical Center, San Diego, CA, USA
    Exp Mol Med 38:191-5. 2006
    ..These findings make the alpha4-paxillin interaction a potentially attractive therapeutic target in controlling leukocyte trafficking...
  35. ncbi Rapid recruitment of inflammatory monocytes is independent of neutrophil migration
    Robert B Henderson
    Leukocyte Adhesion Laboratory, Cancer Research United Kingdom London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    Blood 102:328-35. 2003
    ..The murine monocyte therefore responds rapidly to chemokines produced in situ by tissue cells at the site of inflammation with no requirement for prior influx of neutrophils...
  36. ncbi Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?
    Richard J Davenport
    Global Chemistry, UCB Group, Granta Park, Great Abington, Cambridge CB16GS, UK
    Drug Discov Today 12:569-76. 2007
    ..Recent advances in small molecule development are worth reviewing. New understanding of pharmacokinetics and selectivity will potentially contribute to the development of alpha4 antagonist with greater clinical efficacy and safety...
  37. 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...
  38. ncbi Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells
    A Puig-Kroger
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain Servicio de Inmuno Oncología, Hospital Universitario Gregorio Maranon, Madrid, Spain
    J Immunol 165:4338-45. 2000
    ..The differential expression of CD49d on immature and mature MDDC might contribute to their distinct motility capabilities and mediate mature DC migration into lymphoid organs...
  39. 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...
  40. ncbi Analysis of the roles of RGD-binding integrins, alpha(4)/alpha(9) integrins, alpha(6) integrins, and CD9 in the interaction of the fertilin beta (ADAM2) disintegrin domain with the mouse egg membrane
    Xiaoling Zhu
    Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD 21205, USA
    Biol Reprod 66:1193-202. 2002
    ....
  41. 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
    ....
  42. ncbi Alpha 4 integrin-dependent leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation
    B Johnston
    Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
    J Immunol 164:3337-44. 2000
    ..These findings provide the first evidence that alpha 4 beta 1 integrin-dependent leukocyte rolling and adhesion can occur in vivo via a mechanism other than VCAM-1...
  43. ncbi CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL
    Aneela Majid
    Medical Research Council MRC Toxicology Unit, University of Leicester, Leicester, UK
    Leuk Res 35:750-6. 2011
    ..Taken together, our data support the introduction of CD49d into routine immunophenotyping panels for CLL and indicate that the therapeutic targeting of this molecule may prove useful in this disease...
  44. pmc An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration
    Nicholas O Deakin
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    J Cell Sci 122:1654-64. 2009
    ..Taken together, these data identify a key signalling nexus mediating alpha4 integrin-dependent migration...
  45. ncbi DcR3 protects THP-1 macrophages from apoptosis by increasing integrin alpha4
    Koji Tateishi
    Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
    Biochem Biophys Res Commun 389:593-8. 2009
    ..Undifferentiated THP-1 cells were also induced to form aggregates by DcR3-Fc. The expression of integrin alpha4 was significantly increased by DcR3-Fc...
  46. ncbi CpG island hypermethylation of E-cadherin (CDH1) and integrin alpha4 is associated with recurrence of early stage esophageal squamous cell carcinoma
    Eun Ju Lee
    Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
    Int J Cancer 123:2073-9. 2008
    ..We retrospectively analyzed the CpG island hypermethylation of the p16, Wif-1, sFRP1, integrin alpha4, CDH1, DAP kinase and RARbeta2 genes in 251 ESCCs...
  47. 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...
  48. ncbi Adhesion molecules are promising candidates to establish surrogate markers for natalizumab treatment
    P Wipfler
    Paracelsus Medical University, Christian Doppler Klinik, University Hospital of Neurology, Salzburg, Austria
    Mult Scler 17:16-23. 2011
    ..Its therapeutic mechanism is the blockade of the α4-integrin subunit of the adhesion molecule (AM) very late activation antigen-4 (VLA-4), which leads to an inhibition of immune cell extravasation into the central nervous system (CNS)...
  49. pmc Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of alpha4 integrin- and CXCR4-mediated engraftment in NOD/SCID beta2-microglobulin-null mice
    Jacques Foguenne
    GIGA Research, Hematology Unit, University of Liege, Belgium
    Haematologica 94:185-94. 2009
    ..We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in engraftment of unmanipulated and cytokine-treated human cord blood CD34(+) cells...
  50. ncbi Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells
    Olivier Giet
    Department of Medicine Hematology, University of Liege, CHU Sart Tilman B35, 13 avenue de l Hôpital, B 4000 Liege, Belgium
    Blood 99:2023-31. 2002
    ..In addition, alpha4 and alpha5 integrin functions are independently modulated during cell cycle transit...
  51. ncbi Evaluation of the anti-HIV activity of natalizumab, an antibody against integrin alpha4
    Eduardo Pauls
    Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain
    AIDS 23:266-8. 2009
    ..However, natalizumab failed to block the replication of HIV-1 strains in lymphoid MT-4 cells or CD4+ T cells at concentrations up to 125microg/ml. Our results suggest that alpha4 integrins are not essential cofactors for HIV replication...
  52. pmc Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle
    J T Yang
    Howard Hughes Medical Institute Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Cell Biol 135:829-35. 1996
    ..Taking these results together, we conclude that alpha 4 integrins appear not to play essential roles in normal skeletal muscle development...
  53. ncbi CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphocytic leukemia cell survival
    Antonella Zucchetto
    Clinical and Experimental Onco Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
    Cancer Res 69:4001-9. 2009
    ..Altogether, CD38 and CD49d can be thought of as parts of a consecutive chain of events ultimately leading to improved survival of CLL cells...
  54. ncbi A fragment of paxillin binds the alpha 4 integrin cytoplasmic domain (tail) and selectively inhibits alpha 4-mediated cell migration
    Shouchun Liu
    Department of Vascular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:20887-94. 2002
    ..Thus, paxillin binding to the alpha(4) tail leads to enhanced cell migration and inhibition of the alpha(4)-paxillin interaction selectively blocks the alpha4-dependent cellular responses...
  55. ncbi Natalizumab for multiple sclerosis
    Richard M Ransohoff
    Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute and Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, OH 44195, USA
    N Engl J Med 356:2622-9. 2007
  56. ncbi The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes
    Kathleen J Till
    Department of Haematology, University of Liverpool, Liverpool, United Kingdom
    Blood 99:2977-84. 2002
    ..The present studies are the first to shed light on the factors determining CLL cell entry into nodes and define the phenotype of circulating malignant cells likely to determine the pattern of lymph node enlargement in the disease...
  57. ncbi An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells
    Naoyuki Nishiya
    Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0726, USA
    Nat Cell Biol 7:343-52. 2005
    ..These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration...
  58. pmc NG2, a novel proapoptotic receptor, opposes integrin alpha4 to mediate anoikis through PKCalpha-dependent suppression of FAK phosphorylation
    N E Joo
    Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109 1078, USA
    Cell Death Differ 15:899-907. 2008
    ..We found that an altered FN matrix induced anoikis in fibroblasts by upregulating NG2 and downregulating integrin alpha4. Suppressing NG2 expression or overexpressing alpha4 rescued cells from anoikis...
  59. ncbi Alpha4 integrins as therapeutic targets in autoimmune disease
    Ulrich H von Andrian
    N Engl J Med 348:68-72. 2003
  60. pmc Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels
    P Vajkoczy
    Department of Neurosurgery, Klinikum Mannheim, Universitat Heidelberg, Mannheim, Germany
    J Clin Invest 108:557-65. 2001
    ....
  61. pmc On the adaptation of endosteal stem cell niche function in response to stress
    Yi Jiang
    University of Washington, Department of Medicine Hematology, Seattle, WA 98195, USA
    Blood 114:3773-82. 2009
    ..A similar phenotype was observed with cells rendered G(i)-protein signaling incompetent by pertussis toxin treatment, supporting an active stromal-derived factor 1 (SDF-1) gradient near endosteum after irradiation...
  62. ncbi Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteins
    Chinten James Lim
    Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
    Nat Cell Biol 9:415-21. 2007
    ....
  63. ncbi Natalizumab: targeting alpha4-integrins in multiple sclerosis
    Britta Engelhardt
    Theodor Kocher Institute, University of Bern, Bern, Switzerland
    Neurodegener Dis 5:16-22. 2008
    ..In this review, we discuss the basic mechanism of action, key clinical results of clinical trials and the emerging indication of natalizumab in MS...
  64. ncbi A safety and pharmacokinetic study of intravenous natalizumab in patients with MS
    W A Sheremata
    University of Miami, Department of Neurology, School of Medicine, FL 33136, USA
    Neurology 52:1072-4. 1999
    ..All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies...
  65. ncbi Effect of antibody against integrin alpha4 on bleomycin-induced pulmonary fibrosis in mice
    Q Wang
    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    Biochem Pharmacol 60:1949-58. 2000
    ..In this study, we tested the hypothesis that neutralizing antibody for integrin alpha4 (PS2) may reduce bleomycin (BL)-induced lung fibrosis in vivo...
  66. ncbi Anti-adhesion molecule therapies in inflammatory bowel disease: touch and go
    Tommaso Stefanelli
    Division of Gastroenterology, Istituto Clinico Humanitas, IRCCS in Gastroenterology, Viale M lt anzoni, Rozzano, Milan, Italy
    Autoimmun Rev 7:364-9. 2008
    ..This review outlines the scientific basis behind this therapeutic approach, and describes the principal clinical studies that have been carried out on these new molecules in patients with IBD...
  67. pmc The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1
    Y Taooka
    Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, California 94143, USA
    J Cell Biol 145:413-20. 1999
    ..These observations suggest a possible role for alpha9beta1/VCAM-1 interactions in extravasation of neutrophils at sites of acute inflammation...
  68. pmc Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit
    Christopher C DeNucci
    Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    J Immunol 184:2458-67. 2010
    ..Thus, the preferential association of beta1 integrin with alpha4 integrin suppresses alpha4beta7 integrin expression and regulates the localization of memory CD4 T cells...
  69. ncbi Direct observations in vivo on the role of endothelial selectins and alpha(4) integrin in cytokine-induced leukocyte-endothelium interactions in the mouse aorta
    E E Eriksson
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Circ Res 86:526-33. 2000
    ....
  70. ncbi Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin
    William J Sandborn
    Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Gastroenterol 98:2372-82. 2003
    ....
  71. ncbi Aberrant DNA methylation of integrin alpha4: a potential novel role for metastasis of cholangiocarcinoma
    Kyung Ok Uhm
    Department of Anatomy, Institute of Human Genetics, Brain Korea 21 Biomedical Sciences, Korea University College of Medicine, 126 1, Anam Dong 5 Ga, Seongbuk gu, Seoul, 136 705, Republic of Korea
    J Cancer Res Clin Oncol 136:187-94. 2010
    Although the altered expression of integrin alpha4 is known to be associated with transformation or metastasis in several human cancers, the information on cholangiocarcinoma (CC) is still poor...
  72. ncbi Paxillin binding to the alpha 4 integrin subunit stimulates LFA-1 (integrin alpha L beta 2)-dependent T cell migration by augmenting the activation of focal adhesion kinase/proline-rich tyrosine kinase-2
    David M Rose
    Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Immunol 170:5912-8. 2003
    ....
  73. ncbi Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo
    A Hamann
    Department of Immunology, University Hospital of Eppendorf, Hamburg, Germany
    J Immunol 152:3282-93. 1994
    ..The results support a major, but not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to mucosal sites...
  74. ncbi Reevaluation of P-selectin and alpha 4 integrin as targets for the treatment of experimental autoimmune encephalomyelitis
    Steven M Kerfoot
    Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
    J Immunol 176:6225-34. 2006
    ..Despite evidence of a similar ability to block firm adhesion, Abs to P-selectin had no effect. Importantly, combined blockade of both adhesion molecules resulted in significantly better clinical outcome than anti-alpha(4) integrin alone...
  75. ncbi Emigrated neutrophils regulate ventricular contractility via alpha4 integrin
    B Y Poon
    Department of Physiology and Biophysics and Immunology Research Group, University of Calgary, Calgary, Alberta, Canada
    Circ Res 84:1245-51. 1999
    ..In contrast, immunosuppression of the alpha4 integrin alone was sufficient to dramatically reduce all parameters of cell dysfunction measured in this study...
  76. ncbi Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor-induced adhesion molecule expression on eosinophils by p38 mitogen-activated protein kinase and nuclear factor-[kappa] B
    Chun K Wong
    Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
    Am J Respir Cell Mol Biol 29:133-47. 2003
    ..These cytokines therefore play a crucial role, via the p38 MAPK and NF-kappaB pathways, in the expression of important adhesion molecules on eosinophils in allergic inflammation...
  77. pmc FRET detection of cellular alpha4-integrin conformational activation
    Alexandre Chigaev
    Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    Biophys J 85:3951-62. 2003
    ..The coordination between the extension of alpha4-integrin and its affinity provides a mechanism for Dembo's catch-bond concept...
  78. ncbi Functional differences between integrin alpha4 and integrins alpha5/alphav in modulating the motility of human oral squamous carcinoma cells in response to the V region and heparin-binding domain of fibronectin
    Yan Zhang
    Department of Stomatology, School of Dentistry, University of California, San Francisco, CA 94102, USA
    Exp Cell Res 295:48-58. 2004
    ..Thus, the increased motility induced by the FN protein is probably mediated by alphav and alpha5, whereas alpha4 downregulates this process in a transdominant fashion...
  79. ncbi Aberrant methylation of integrin alpha4 gene in human gastric cancer cells
    Jinah Park
    National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110 744, Korea
    Oncogene 23:3474-80. 2004
    ..It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers...
  80. ncbi Inhibitors of cell migration that inhibit intracellular paxillin/alpha4 binding: a well-documented use of positional scanning libraries
    Yves Ambroise
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 9:1219-26. 2002
    Screening combinatorial libraries for inhibition of Paxillin binding to the cytoplasmic tail of the integrin alpha4 provided the first inhibitors of this protein-protein interaction implicated in enhanced rates of cell migration and ..
  81. ncbi Stable expression of VLA-4 and increased maturation of the beta 1-integrin precursor after transfection of CHO cells with alpha 4m cDNA
    M Jaspers
    Center for Human Genetics, University of Leuven, Belgium
    FEBS Lett 353:239-42. 1994
    ..These results support the hypothesis that degradation of precursor beta 1 is at least partly determined by the quantity of alpha subunits available intracellulary for heterodimer formation...
  82. ncbi Tysabri raises alarm bells on drug class
    Cormac Sheridan
    Nat Biotechnol 23:397-8. 2005
  83. ncbi New approaches to blockade of alpha4-integrins, proven therapeutic targets in chronic inflammation
    Christiane Kummer
    Department of Medicine, University of California San Diego, 9500 Gilman Drive 0726, La Jolla, CA 92093, USA
    Biochem Pharmacol 72:1460-8. 2006
    ..Thus, blockade of alpha4-integrin signaling may offer a novel strategy for interfering with the functions of these receptors in pathological events while sparing important physiological functions...
  84. pmc Lack of alpha4 integrin expression in stem cells restricts competitive function and self-renewal activity
    Gregory V Priestley
    University of Washington, Department of Medicine Division of Hematology, Box 357710, Seattle, WA 98195 7710
    Blood 107:2959-67. 2006
    ..Collectively, our data provide compelling evidence that under regenerative stress alpha4 integrin assumes a greater importance than for maintenance of steady-state hematopoiesis...
  85. ncbi Guanylate binding protein-1 inhibits spreading and migration of endothelial cells through induction of integrin alpha4 expression
    Kristina Weinländer
    Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany
    FASEB J 22:4168-78. 2008
    ..Endothelial cell migration is a key process during angiogenesis. Therefore, ITGA4 may be a novel molecular target to modulate angiogenesis in human disease...
  86. ncbi Molecular mechanisms underlying IL-4-induced leukocyte recruitment in vivo: a critical role for the alpha 4 integrin
    M J Hickey
    Immunology Research Group, University of Calgary, Alberta, Canada
    J Immunol 163:3441-8. 1999
    ....
  87. ncbi Role of alpha4 integrin and VCAM-1 in CD18-independent neutrophil migration across mouse cardiac endothelium
    Robert A Bowden
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD, USA
    Circ Res 90:562-9. 2002
    ..We conclude tissue-specific differences in endothelial cells account, at least partially, for CD18-independent neutrophil infiltration in the heart...
  88. pmc alpha(4)-integrin mediates neutrophil-induced free radical injury to cardiac myocytes
    B Y Poon
    Immunology Research Group, University of Calgary, Calgary, Alberta T2N 1N4, Canada
    J Cell Biol 152:857-66. 2001
    ....
  89. ncbi Expanding roles for alpha 4 integrin and its ligands in development
    A M Sheppard
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110
    Cell Adhes Commun 2:27-43. 1994
    ..Finally, based on their patterns of expression, we conclude that VCAM-1 only participates in a subset of interactions involving alpha 4 integrins, whereas FN appears to be the more general ligand...
  90. ncbi Synergistic effect of TNF-alpha in soluble VCAM-1-induced angiogenesis through alpha 4 integrins
    Shintaro Nakao
    Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    J Immunol 170:5704-11. 2003
    ..These results suggest that sVCAM-1/alpha(4) integrin induces angiogenesis through p38 and FAK signaling pathways...
  91. ncbi Vascular cell adhesion molecule-Ig fusion protein selectively targets activated alpha 4-integrin receptors in vivo. Inhibition of autoimmune diabetes in an adoptive transfer model in nonobese diabetic mice
    A Jakubowski
    Biogen, Inc, Cambridge, MA 02142, USA
    J Immunol 155:938-46. 1995
    ..Thus, soluble VCAM-Ig can modify alpha 4-dependent disease progression, apparently by its selective action on cells with activated alpha 4-integrin receptors, thereby providing evidence for distinct alpha 4 activation states in vivo...
  92. ncbi An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter
    G D Rosen
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110
    J Biol Chem 269:15652-60. 1994
    ..This arrangement of Ets sites, coupled with the tissue- and developmental-specific expression of Ets members, likely play a key role in defining the pattern of alpha 4 integrin...
  93. ncbi Effect of interleukin-13 or tumor necrosis factor-alpha on eosinophil adhesion to endothelial cells under physiological flow conditions
    Hiroshi Tachimoto
    Department of Allergy, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Japan
    Int Arch Allergy Immunol 143:33-7. 2007
    ..We examined the mechanisms used by eosinophils to accumulate on IL-13- or TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs) under flow conditions...
  94. ncbi Monocyte adhesion to xenogeneic endothelium during laminar flow is dependent on alpha-Gal-mediated monocyte activation
    Mark D Peterson
    Division of Cardiac Surgery, Department of Surgery, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
    J Immunol 174:8072-81. 2005
    ..Thus, activation of monocyte beta(2) integrins by alpha-gal expressed on xenogeneic endothelium provides a mechanism that may explain the dramatic accumulation of monocytes in vivo...
  95. ncbi CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow
    Alice Miles
    Liver Research Group, Medical Research Council Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
    Am J Physiol Gastrointest Liver Physiol 294:G1257-67. 2008
    ....
  96. ncbi Rules of recruitment for Th1 and Th2 lymphocytes in inflamed liver: a role for alpha-4 integrin and vascular adhesion protein-1
    Claudine S Bonder
    Immunology Research Group, Department Physiology and Biophysics, University of Calgary, Alberta, Canada
    Immunity 23:153-63. 2005
    ..While this may still be true for neutrophils, Th1 and Th2 cells use alpha(4)-integrin and VAP-1, respectively, to adhere within the liver sinusoids...
  97. ncbi CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity
    Chanchal Sadhu
    ICOS Corporation, 22021 20th Ave, S E, Bothell, WA 98021, USA
    J Leukoc Biol 81:1395-403. 2007
    ..The CD11c-binding site on VCAM-1 appears to be different from that used by the integrin alpha4. CD11c and alpha4beta1 contributed to monocyte capture and transmigration on inflamed human aortic ..
  98. ncbi LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue
    Huaxin Duan
    National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, 87 Xiang Ya Road, Changsha, Hunan, 410008, China
    Thromb Haemost 96:807-15. 2006
    ..These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues...
  99. ncbi Role of alpha4 integrin and its ligand VCAM-1 in the specific extravasation of a tumor-specific TH2 clone into tumor tissue that initiates its rejection
    Zhe Jin
    Department of Immunology, Kochi Medical School, Nankoku Shi, Kochi, Japan
    Int J Cancer 111:558-67. 2004
    ..It is likely that this initial migration of specific CD4(+) T cells into tumor tissues promotes the subsequent infiltration into the tumor of other immunocytes that effect tumor destruction...
  100. ncbi Quantitative expression of the major homing integrins alphaL and alpha4 on human cord blood hematopoietic progenitor and stem cells
    F Mastrandrea
    Allergy and Clinical Immunology O U, SS Annunziata Hospital, AUSL TA1, Taranto, Italy
    Eur Ann Allergy Clin Immunol 36:211-4. 2004
    ..5), suggesting a preferential usage of the homing axis VLA-4/VCAM-1. Results consistency with outcomes of clinical trials that relate SLIT efficacy to allergen dosage is discussed...
  101. ncbi IVIg therapy in brain inflammation: etiology-dependent differential effects on leucocyte recruitment
    Benoit M Lapointe
    Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
    Brain 127:2649-56. 2004
    ..We also report that IVIg will not be beneficial in all types of pro-adhesive states and may in fact be detrimental in a situation such as stroke...

Research Grants51

  1. FIBRONECTIN REGULATION OF CARCINOMA APOPTOSIS
    Yvonne Kapila; Fiscal Year: 2009
    ..These studies will help explain some of the cell-matrix interactions and signaling mechanisms that regulate tumor cell biology, and may provide insights into the pathogenesis of oral SCC. ..
  2. Role of alpha4-paxillin signaling in lymphangiogenesis
    CHRISTIE AVRAAMIDES; Fiscal Year: 2010
    ..Understanding how the lymph nodes prepare and permit for this tumor metastasis, will enable new therapies to be developed for treating and/or preventing metastases. ..
  3. 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. ..
  4. Selectin Control of Leukocyte Adhesion in Shear
    Michael Lawrence; Fiscal Year: 2006
    ..Such insight may lead to identification of more effective molecular targets for anti-inflammatory therapeutics. ..
  5. A4B7 INTEGRIN IN INTESTINAL INFLAMMATION AND IMMUNITY
    Eugene Butcher; Fiscal Year: 1999
    ..They may lead to novel approaches to regulating pathologic immune and inflammatory reactions in inflammatory bowel disease. ..
  6. 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. ..
  7. VCAM 1 EXPRESSION IN ENDOTHELIAL CELLS
    Douglas Dean; Fiscal Year: 1999
    ..We propose studies to examine the molecular mechanisms of how this "allergic cytokine" combination regulates VCAM-1 expression. ..
  8. SPECIFIC INTEGRIN ALPHA 4 CYTOPLASMIC TAIL FUNCTIONS
    MARTIN HEMLER; Fiscal Year: 1999
    DESCRIPTION (Adapted from the Applicant's Abstract): The cytoplasmic domain of the integrin alpha4 subunit differs markedly from other alpha chain cytoplasmic domains with respect to focal adhesion formation, and this may account for ..
  9. ZEB IN LEUKOCYTE DIFFERENTIATION AND FUNCTION
    Douglas Dean; Fiscal Year: 2002
    ..It is our aim in the future to apply the basic science information that we gain from the studies on ZEB activity to regulate leukocyte differentiation and function in inflammatory diseases. ..
  10. Vascular responses in transgenic sickle cell mice
    Beatrice Gee; Fiscal Year: 2007
    ..Co-mentors, Drs. Freeman and Townes at Univ. of Alabama, Birmingham, are also experts in their fields. ..
  11. PATHWAY OF VENTRICULAR MORPHOGENESIS MEDICATED BY RXRA
    Henry Sucov; Fiscal Year: 2001
    ..abstract_text> ..
  12. INTRAPULMONARY ADHESION BLOCKADE IN ASTHMA
    John Harlan; Fiscal Year: 2002
    ..These studies address previously unexplored areas of integrin biology and pulmonary immune responses and have the potential to suggest new approaches to therapy in asthma. ..
  13. Case/Cleveland Clinic Clinical Research Training Program (RMI)
    Richard Rudick; Fiscal Year: 2007
    ..It will host a national conference on this theme during 2007 to exchange "lessons learned" and evaluate how NIH-sponsored programs are measuring up to this strategic goal. [unreadable] [unreadable]..
  14. Case/Cleveland Clinical Research Training Program (RMI)
    Richard Rudick; Fiscal Year: 2004
    ..It will host a national conference on this theme during 2007 to exchange "lessons learned" and evaluate how NIH-sponsored programs are measuring up to this strategic goal. ..
  15. EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT PROGRAM GCRC
    Richard Rudick; Fiscal Year: 2003
    ..The expected outcome of this construction project will be a centralized facility to conduct innovative, collaborative clinical research protocols and train a new generation of physician scientists. ..
  16. HIV Neuroprotection Workshop
    Joseph Berger; Fiscal Year: 2004
    ..The proposed conference is the first of its kind to highlight neuroprotection in HIV CNS and PNS disorders. By coupling this meeting with the International Symposium on Neurovirology this synergy can be exploited. ..
  17. JCV Virus Expression in Oropharynx and HIV
    Joseph Berger; Fiscal Year: 2004
    ..This line of investigation would add credence to an oropharyngeal mechanism of JCV transmission and may ultimately lead to the clinical identification of an acute illness attributable to this pathogen. ..
  18. 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. ..
  19. Pregnancy and the Modulation of Multiple Sclerosis
    Annette Langer Gould; Fiscal Year: 2006
    ..The search for the pregnancy-related factor or hormone responsible for the protective effect of pregnancy in MS may potentially lead to the development of novel treatments for MS and other Th1-driven autoimmune diseases. ..
  20. MR PREDICTORS OF RESPONSE TO HAART IN HIV DEMENTIA
    Joseph Berger; Fiscal Year: 2004
    ..It will also open novel avenues for exploring the differential sensitivities of these pathways to HAART, and suggest unique therapeutic options. ..
  21. 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. ..
  22. GLOBIN SWITCHING AND ERYTHROID DIFFERENTIATION
    Thalia Papayannopoulou; Fiscal Year: 2002
    ....
  23. 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. ..
  24. 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. ..
  25. 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. ..
  26. Brain Atrophy/Diffusion Tensor Study/Multiple Sclerosis
    Robert Fox; Fiscal Year: 2008
    ..Furthermore, these studies should help develop improved methods for evaluating new therapeutic strategies for neuroprotection and neuroregeneration. ..
  27. OSCCAR: A Novel, Population-based Prospective Inception Cohort of Inflammatory Bo
    BRUCE SANDS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  28. Novel Dendritic Cell Chemoattractant and Receptor
    Eugene Butcher; Fiscal Year: 2009
    ..abstract_text> ..
  29. MOLECULAR MECHANISMS OF CD4+ T CELL DYSFUNCTION IN SIV
    Aftab Ansari; Fiscal Year: 2009
    ..abstract_text> ..
  30. IMMUNOMODULATION IN INFLAMMATORY BOWEL DISEASE
    BRUCE SANDS; Fiscal Year: 2004
    ..The principal investigator seeks to become an independent clinical investigator by completing the didactic and scientific portions of this proposal. ..
  31. Gender differences in immune responses in MS
    Richard Ransohoff; Fiscal Year: 2009
    ....
  32. Intestinal Lymphocyte Trafficking
    Eugene Butcher; Fiscal Year: 2009
    ....
  33. CHEMOATTRACTANT SIGNALING TO LEUKOCYTE INTEGRINS
    Eugene Butcher; Fiscal Year: 2001
    ..These studies should define signaling mechanisms regulating the adhesion of leukocytes and other cells, and may lead to novel therapeutic approaches for the control of neoplastic and inflammatory diseases ..
  34. CNS antigen sensitization in stroke.
    Kyra Becker; Fiscal Year: 2009
    ..Data derived from this study will be used to plan future trials of immunomodulation in patients with stroke. ..
  35. Tolerogenic DC as Therapeutic Agents in GVHD
    Eugene C Butcher; Fiscal Year: 2010
    ..Together, these studies will define in detail the potential of CCR9+ pDCs to suppress deleterious effects of GVHD in settings modeling situations in which human patients encounter pathogenic GVHD responses. ..
  36. ENDOTHELIAL CELL BIOLOGY IN INFLAMMATION
    Eugene Butcher; Fiscal Year: 2008
    ..The proposed studies should expand our understanding of the critical role of the vascular endothelium in regulating lymphocyte trafficking during normal and pathologic immune responses. ..
  37. VASCULAR-MONOCYTE ADHESION MOLECULE IN ATHEROGENESIS
    Eugene Butcher; Fiscal Year: 2002
    ..The proposed studies will elucidate the structure of this novel vascular receptor and its role in monocyte recruitment in atherogenesis. They may lead to new approaches to the regulation of the atherogenic process. ..
  38. A Phase I/II Trial of a Therapeutic HPV Vaccine
    Cornelia Trimble; Fiscal Year: 2004
    ....
  39. THE ROLE OF LYMPHOCYTES IN CEREBRAL ISCHEMIC INJURY
    Kyra Becker; Fiscal Year: 2004
    ....
  40. THERAPEUTIC VACCINES FOR HPV DISEASES
    Cornelia Trimble; Fiscal Year: 2005
    ..These facilities will be used to develop Dr. Trimble's ability to design and execute clinical trials evaluating preneoplastic HPV-associated lesions of the female lower genital tract. ..
  41. CD4 T Cell Activation in SIV+Disease Resistant Mangabeys
    Aftab Ansari; Fiscal Year: 2004
    ..abstract_text> ..
  42. Conference on Leukocyte Trafficking
    Eugene Butcher; Fiscal Year: 2004
    ..abstract_text> ..
  43. B CLL SUBGROUPS--MATURATION STAGE AND GENE EXPRESSION
    Nicholas Chiorazzi; Fiscal Year: 2004
    ..Hopefully, these differences will provide important basic and clinical insights into this disease and suggest future prognostic and therapeutic approaches to it. ..
  44. Role of T Cell Immunity in Primate AIDS
    Aftab Ansari; Fiscal Year: 2006
    ....
  45. EXTRAVASCULAR TRAFFICKING OF HIV+ CELLS AND PROGNOSIS
    Holly Birdsall; Fiscal Year: 2003
    ....
  46. IMURAN Dose Ranging Study in Crohn's Disease
    BRUCE SANDS; Fiscal Year: 2005
    ..Abstract Not Provided ..
  47. Induction of hepatic tolerance to parasitic nematodes
    Susan Bliss; Fiscal Year: 2007
    ..The research emphasis of the Institute is directed towards animal models of disease, providing a highly supportive environment for the applicant's career development. ..
  48. HIV INFECTION/COCAINE EFFECT ON CARDIOVASCULAR PATHOLOGY
    Aftab Ansari; Fiscal Year: 2003
    ..We reason that such studies may provide unique insights on the relationship between the effects of cocaine and HIV infection in the pathogenesis of cardiovascular disease. ..
  49. Therapeutic DNA-MVA prime boost vaccination for HPV disease
    Cornelia Trimble; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. CELLULAR TRAFFICKING TO INFLAMED FEMALE GENITAL MUCOSA
    Kathleen Kelly; Fiscal Year: 2007
    ..Insight into CXCL13 secretion will impact public health and the welfare of women in the US by aiding the development of therapeutics to prevent tubal infertility. ..