lymphocyte function associated antigen 1

Summary

Summary: An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.

Top Publications

  1. ncbi Dynamic regulation of LFA-1 activation and neutrophil arrest on intercellular adhesion molecule 1 (ICAM-1) in shear flow
    Aaron F H Lum
    Department of Biomedical Engineering, University of California, Davis, California 95616, USA
    J Biol Chem 277:20660-70. 2002
  2. pmc Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow
    Mika Shimonaka
    Bayer Chair, Dept of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 161:417-27. 2003
  3. ncbi Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration
    Z M Ding
    Speros P Martel Laboratory of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    J Immunol 163:5029-38. 1999
  4. ncbi Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes
    Y van Kooyk
    Division of Immunology, The Netherlands Cancer Institute
    Nature 342:811-3. 1989
  5. ncbi RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 4:741-8. 2003
  6. ncbi Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
    Motomu Shimaoka
    The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 112:99-111. 2003
  7. ncbi Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes
    N Oppenheimer Marks
    Harold C Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern, Medical Center, Dallas 75235
    J Immunol 147:2913-21. 1991
  8. pmc Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1
    Jean Francois Giguere
    Research Center in Infectious Diseases, RC709, CHUL Research Center and Faculty of Medicine, Laval University, Quebec, Canada G1V 4G2
    J Virol 78:12062-5. 2004
  9. pmc Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms
    Susanna C Fagerholm
    Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN 00014 Helsinki, Finland
    J Cell Biol 171:705-15. 2005
  10. ncbi JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes
    Georg Ostermann
    Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany
    Nat Immunol 3:151-8. 2002

Research Grants

  1. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
  2. LFA-1 in Lymphocyte Migration
    Minsoo Kim; Fiscal Year: 2013
  3. Migration of polyomavirus JC across the blood-brain-barrier
    Vivek Nerurkar; Fiscal Year: 2009
  4. LYMPHOCYTE FUNCTION ASSOCIATED ANTIGENS
    Timothy A Springer; Fiscal Year: 2013
  5. Protein-mediated molecular adhesion: AFM studies
    VINCENT MOY; Fiscal Year: 2006
  6. Integrin LFA-1 antagonists
    Motomu Shimaoka; Fiscal Year: 2009
  7. UCSD Hillcrest Flow Cytometer
    Paul Mills; Fiscal Year: 2003
  8. SYMPATHETIC NERVOUS SYSTEM REGULATION OF CELL ADHESION
    Paul J Mills; Fiscal Year: 2010
  9. Chemokine Receptor Chimeras by Synthetic Gene Library
    Michael Dustin; Fiscal Year: 2007
  10. Inverted two photon laser scanning microscope for host defense
    Michael Dustin; Fiscal Year: 2008

Detail Information

Publications289 found, 100 shown here

  1. ncbi Dynamic regulation of LFA-1 activation and neutrophil arrest on intercellular adhesion molecule 1 (ICAM-1) in shear flow
    Aaron F H Lum
    Department of Biomedical Engineering, University of California, Davis, California 95616, USA
    J Biol Chem 277:20660-70. 2002
    ..The data reveal that the number of chemotactic receptors bound and the topography and lifetime of high affinity LFA-1 tightly regulate the efficiency of neutrophil capture on ICAM-1...
  2. pmc Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow
    Mika Shimonaka
    Bayer Chair, Dept of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 161:417-27. 2003
    ..Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation...
  3. ncbi Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration
    Z M Ding
    Speros P Martel Laboratory of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    J Immunol 163:5029-38. 1999
    ..Neutrophil extravasation in response to TNF-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased...
  4. ncbi Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes
    Y van Kooyk
    Division of Immunology, The Netherlands Cancer Institute
    Nature 342:811-3. 1989
    ..We postulate that CD2 and CD3 can differentially regulate the affinity of LFA-1 for its ligands by modulating its molecular conformation through PKC-dependent mechanisms...
  5. ncbi RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501 Japan
    Nat Immunol 4:741-8. 2003
    ..Triggered by activated Rap1, RAPL associated with LFA-1 and rapidly relocated to the leading edge and accumulated at immunological synapses. Thus, RAPL regulates lymphocyte adhesion through the spatial distribution of LFA-1...
  6. ncbi Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
    Motomu Shimaoka
    The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 112:99-111. 2003
    ..Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity...
  7. ncbi Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes
    N Oppenheimer Marks
    Harold C Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern, Medical Center, Dallas 75235
    J Immunol 147:2913-21. 1991
    ..Moreover, ICAM-1 but not VCAM-1 plays a role in transendothelial migration, regardless of the receptor-counter-receptor pairs used for initial binding...
  8. pmc Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1
    Jean Francois Giguere
    Research Center in Infectious Diseases, RC709, CHUL Research Center and Faculty of Medicine, Laval University, Quebec, Canada G1V 4G2
    J Virol 78:12062-5. 2004
    ..The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection...
  9. pmc Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms
    Susanna C Fagerholm
    Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN 00014 Helsinki, Finland
    J Cell Biol 171:705-15. 2005
    ..Thus, site-specific phosphorylation of the integrin cytoplasmic domains is important for the dynamic regulation of these complex receptors in cells...
  10. ncbi JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes
    Georg Ostermann
    Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany
    Nat Immunol 3:151-8. 2002
    ..Thus, JAM-1 is a counter-receptor for LFA-1 that is ideally situated to guide and control transmigration during leukocyte recruitment...
  11. ncbi Avidity regulation of integrins: the driving force in leukocyte adhesion
    Y van Kooyk
    Department of Tumor Immunology, University Medical Center Nijmegen, St Radboud, P Van Leydenlaan 25, 6525 EX, The, Nijmegen, Netherlands
    Curr Opin Cell Biol 12:542-7. 2000
    ....
  12. pmc Molecular anatomy of antigen-specific CD8(+) T cell engagement and synapse formation in vivo
    Dorian B McGavern
    Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Immunol 3:918-25. 2002
    ..In addition, we have established an in vivo approach for assessing the intricacies of antigen-specific T cell activation, migration, engagement, memory and other defining elements of adaptive immunity...
  13. ncbi Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction
    Azucena Salas
    The CBR Institute for Biomedical Research, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115 USA
    Immunity 20:393-406. 2004
    ....
  14. pmc Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1
    F Sanchez-Madrid
    J Exp Med 158:586-602. 1983
    ..Therefore, sites of Mac-1 and LFA-1 involved in their respective adhesion-related functions, as well as distinctive structural features, have been localized to the alpha-subunits...
  15. pmc Organization of the integrin LFA-1 in nanoclusters regulates its activity
    Alessandra Cambi
    Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Mol Biol Cell 17:4270-81. 2006
    ....
  16. 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...
  17. pmc Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice
    T G Diacovo
    The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 187:197-204. 1998
    ..These profound effects of platelet-mediated cell-cell interactions on lymphocyte trafficking and formation of immunologic memory may impact on a variety of autoimmune and inflammatory conditions...
  18. ncbi LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells
    Omar D Perez
    Baxter Laboratory for Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA, USA
    Blood 104:1083-93. 2004
    ..These results identify novel, specific functional consequence of LFA-1-mediated cytolytic activity in perforin-containing human NK subsets...
  19. 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...
  20. ncbi Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site
    G Weitz-Schmidt
    Novartis Pharma AG, Preclinical Research, Basel, Switzerland
    Nat Med 7:687-92. 2001
    ..Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection...
  21. ncbi SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates
    Hongyan Wang
    Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Nat Immunol 4:366-74. 2003
    ..Our findings identify a mechanism by which SKAP-55 modulates T cell responses to antigen...
  22. ncbi Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines
    Revital Shamri
    Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
    Nat Immunol 6:497-506. 2005
    ..These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion...
  23. ncbi Memory T cell populations in the lung airways are maintained by continual recruitment
    Kenneth H Ely
    Trudeau Institute, Saranac Lake, NY 12983, USA
    J Immunol 176:537-43. 2006
    ..These data indicate that peripheral T cell memory is dynamic and depends on a systemic source of T cells...
  24. ncbi HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization
    Juan M Serrador
    Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, E 28006 Madrid, Spain
    Immunity 20:417-28. 2004
    ..Our results underscore the key role for HDAC6 in the organization of the immune synapse and the antigen-specific reorientation of the MTOC...
  25. pmc Importance of integrin LFA-1 deactivation for the generation of immune responses
    Monika Semmrich
    Department of Surgery, Immunology, and Hygiene, Technische Universitat Munchen, 81675 Munich, Germany
    J Exp Med 201:1987-98. 2005
    ..Thus, deactivation of LFA-1 and disassembly of LFA-1-mediated cell contacts seem to be vital for the generation of normal immune responses...
  26. ncbi Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface
    J M Casasnovas
    The Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA
    Nature 387:312-5. 1997
    ..A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens...
  27. pmc Adhesive dynamics simulation of G-protein-mediated chemokine-activated neutrophil adhesion
    Kelly E Caputo
    Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biophys J 96:2989-3004. 2009
    ....
  28. pmc Recruitment of dynein to the Jurkat immunological synapse
    Jeffrey Combs
    Department of Molecular Cell and Developmental Biology, University of Texas, 1 University Station, MC C0930, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 103:14883-8. 2006
    ....
  29. ncbi The role of the CPNKEKEC sequence in the beta(2) subunit I domain in regulation of integrin alpha(L)beta(2) (LFA-1)
    Tetsuji Kamata
    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Immunol 168:2296-301. 2002
    ..These results suggest that the CPNKEKEC sequence of the beta(2) I domain is involved in regulating the alpha(L) I domain...
  30. pmc Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells
    Rogier W Sanders
    Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Virol 76:7812-21. 2002
    ..The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission...
  31. pmc LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor
    R Schmits
    Amgen Institute, Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada
    J Exp Med 183:1415-26. 1996
    ..Thus CD11a deficiency causes a selective defect in induction of peripheral immune responses whereas responses to systemic infection are normal...
  32. pmc Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade
    Mia Phillipson
    Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary T2N 4N1, Alberta, Canada
    J Exp Med 203:2569-75. 2006
    ..e., LFA-1-dependent adhesion followed by Mac-1-dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature...
  33. ncbi Suppression of human lymphocyte chemotaxis and transendothelial migration by anti-LFA-1 antibody
    D E Van Epps
    Applied Sciences, Baxter Healthcare Corporation, Round Lake, IL 60073
    J Immunol 143:3207-10. 1989
    ..These studies indicate that LFA-1 plays a role in the migration of T cells through HUVEC and in the in vitro chemotactic response of T lymphocytes to IL-2 and LCF...
  34. ncbi LFA-1 contributes an early signal for NK cell cytotoxicity
    Domingo F Barber
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 173:3653-9. 2004
    ..Thus, in contrast to T cells, in which even adhesion through LFA-1 is dependent on signals from other receptors, NK cells receive early activation signals directly through LFA-1...
  35. ncbi Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs)
    David Jimenez
    Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autonoma, 28049 Madrid, Spain
    J Biol Chem 280:5854-61. 2005
    ..N-Linked glycosylation regulate both conformation and immune related functions of ICAM receptors...
  36. pmc Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration
    Sunil K Shaw
    Dept of Pathology, Center for Excellence in Vascular Biology, Brigham and Women s Hospital and Harvard Medical School, 77 Louis Pasteur Ave, Boston, MA 02115, USA
    J Exp Med 200:1571-80. 2004
    ..This is the first demonstration that neutrophil LFA-1 rapidly redistributes to form a ringlike structure that coclusters with endothelial ICAM-1 as the neutrophil transmigrates...
  37. pmc LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse
    Beth Graf
    David H Smith Center for Vaccine Biology and Immunology, University of Rochester, NY 14642, USA
    J Immunol 179:1616-24. 2007
    ....
  38. pmc Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains
    C Lu
    The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:2393-8. 2001
    ..These results suggest that Mn(2+) activates alphaLbeta2 by binding to a site other than the I domain, most likely the I-like domain of beta2...
  39. pmc Adhesion molecule interactions facilitate human immunodeficiency virus type 1-induced virological synapse formation between T cells
    Clare Jolly
    The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom
    J Virol 81:13916-21. 2007
    ..Thus, cognate adhesion molecule interactions at the VS are important for HIV-1 spread between T cells...
  40. ncbi Membrane-proximal signaling events in beta-2 integrin activation
    Bettina Kellersch
    Life and Medical Sciences Institute LIMES, Molecular Immune and Cell Biology Program Unit, Laboratory of Molecular Immunology, University of Bonn, Germany
    Results Probl Cell Differ 43:245-57. 2006
    ..This review will highlight recent developments on transmembrane and intracellular signaling proteins, which have been implicated in beta-2 integrin activation...
  41. ncbi Leukocyte function-associated antigen-1: structure, function and application prospects
    Ma Xingyuan
    State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, P R China
    Protein Pept Lett 13:397-400. 2006
    ..Many different inhibitors (i.e. antibodies, peptides, small molecules) have been demonstrated to block ICAM-1/LFA-1 interaction, and some of them are promising for medical treatment or have reached clinical trials...
  42. ncbi Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling
    Eric Sebzda
    Lymphocyte Activation Laboratory, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Immunol 3:251-8. 2002
    ..This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation...
  43. ncbi Intercellular adhesion molecule-1/LFA-1 ligation favors human Th1 development
    Hermelijn H Smits
    Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, and Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands
    J Immunol 168:1710-6. 2002
    ..This mechanism may be operational during viral infections...
  44. ncbi Rolling of Th1 cells via P-selectin glycoprotein ligand-1 stimulates LFA-1-mediated cell binding to ICAM-1
    Kazuyuki Atarashi
    Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Osaka, Japan
    J Immunol 174:1424-32. 2005
    ..These results support the idea that PSGL-1-mediated rolling interactions induce intracellular signals leading to integrin activation, facilitating Th1 cell arrest and subsequent migration into target tissues...
  45. pmc Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily
    J M Casasnovas
    The Center for Blood Research and Harvard Medical School, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:3017-22. 1999
    ..The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1...
  46. pmc The strict regulation of lymphocyte migration to splenic white pulp does not involve common homing receptors
    Martijn A Nolte
    Department of Molecular Cell Biology, VU University Medical Centre, Amsterdam, The Netherlands
    Immunology 106:299-307. 2002
    ....
  47. ncbi Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1
    Koko Katagiri
    Bayer chair Department of Molecular Immunology and Allergy and Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Biol Chem 279:11875-81. 2004
    ..Our results demonstrate that TCR activation of Rap1 depends on PLC-gamma1. This activity is likely to be mediated by CalDAG-GEFI, which is required to activate LFA-1...
  48. ncbi Cooperation between CD44 and LFA-1/CD11a adhesion receptors in lymphokine-activated killer cell cytotoxicity
    G Matsumoto
    Amgen Institute, and Department of Medical Biophysics and Immunology, University of Toronto, Ontario, Canada
    J Immunol 160:5781-9. 1998
    ..These data also indicate that distinct adhesion receptors cooperate to mediate binding between effector and target cells required for the initiation of "natural" cytotoxicity...
  49. ncbi Cytohesin-1 is a dynamic regulator of distinct LFA-1 functions in leukocyte arrest and transmigration triggered by chemokines
    K S Weber
    Institut für Prophylaxe der Kreislaufkrankheiten, Gene Center, Ludwig Maximilians Universitat, Munich, Germany
    Curr Biol 11:1969-74. 2001
    ....
  50. ncbi LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation
    Yolanda R Carrasco
    Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Immunity 20:589-99. 2004
    ..Thus, LFA-1/ICAM-1 interaction lowers the threshold for B cell activation by promoting B cell adhesion and synapse formation...
  51. ncbi The binding sites for competitive antagonistic, allosteric antagonistic, and agonistic antibodies to the I domain of integrin LFA-1
    Chafen Lu
    CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 173:3972-8. 2004
    ..5 angstroms; maximum, 1.0 angstroms). Agonism by this mAb is thus likely to result from altering the orientation of the I domain with respect to other domains within an intact integrin alphaLbeta2 heterodimer...
  52. ncbi Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins
    Minsoo Kim
    CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Science 301:1720-5. 2003
    ....
  53. pmc Presence of host ICAM-1 in laboratory and clinical strains of human immunodeficiency virus type 1 increases virus infectivity and CD4(+)-T-cell depletion in human lymphoid tissue, a major site of replication in vivo
    Salim Bounou
    Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Quebec, Hôpital CHUL, Ste Foy, Quebec G1V 4G2, Canada
    J Virol 76:1004-14. 2002
    ....
  54. ncbi Integrin-mediated long-term B cell retention in the splenic marginal zone
    Theresa T Lu
    Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Science 297:409-12. 2002
    ..These studies identify key requirements for MZ B cell localization and establish a role for integrins in peripheral lymphoid tissue compartmentalization...
  55. pmc Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1
    Fedde Groot
    Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Retrovirology 3:75. 2006
    ..To corroborate the importance of the ICAM-1- LFA-1 interaction, we performed transmission experiments to LFA-1 negative leukocytes from Leukocyte Adhesion Deficiency type 1 (LAD-1) patients...
  56. ncbi Membranes as messengers in T cell adhesion signaling
    Michael L Dustin
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and the Department of Pathology, NYU School of Medicine, New York, New York 10016, USA
    Nat Immunol 5:363-72. 2004
    ..Speedy delivery of signals may be crucial, and membrane trafficking from endosomes and the Golgi apparatus seem to be essential in delivering the messages from spatially segregated surface receptors...
  57. pmc Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro
    C W Smith
    Speros P Martel Laboratory of Leukocyte Biology, Baylor College of Medicine, Houston, Texas 77054
    J Clin Invest 83:2008-17. 1989
    ..The results in this report indicate that unstimulated neutrophils exhibit LFA-1-dependent attachment to ICAM-1, and chemotactic stimulation enhances the attachment of human neutrophils to ICAM-1 by a Mac-1-dependent process...
  58. ncbi Integrin avidity regulation: are changes in affinity and conformation underemphasized?
    Christopher V Carman
    Center for Blood Research, Harvard Medical School, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115, USA
    Curr Opin Cell Biol 15:547-56. 2003
    ..Recent advances have shed light on the structural basis for affinity regulation and on the signaling mechanisms responsible for both affinity and valency modes of regulation...
  59. ncbi T-cell integrins: more than just sticking points
    Nancy Hogg
    Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK
    J Cell Sci 116:4695-705. 2003
    ..Another important signalling pathway acts through CasL/Crk, which might regulate the activity of the GTPases Rac and Rap1 that have important roles in T-cell migration...
  60. ncbi T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1
    M L Dustin
    Center for Blood Research, Boston, Massachusetts
    Nature 341:619-24. 1989
    ..The increase in avidity is rapid and transient, providing a dynamic mechanism for antigen-specific regulation of lymphocyte adhesion and de-adhesion...
  61. ncbi Activation of leukocyte beta2 integrins by conversion from bent to extended conformations
    Noritaka Nishida
    CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 25:583-94. 2006
    ..The results establish an intimate relationship between extension of beta(2) integrins and their activation in immune responses and leukocyte trafficking...
  62. ncbi Regulation of LFA-1 activity through cytoskeleton remodeling and signaling components modulates the efficiency of HIV type-1 entry in activated CD4+ T lymphocytes
    Mélanie R Tardif
    Research Center in Infectious Diseases, Centre Hospitalier de l Université Laval CHUL Research Center, and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Quebec, Canada G1V 4G2
    J Immunol 175:926-35. 2005
    ..Overall, these data provide new insights into the complex molecular events involved in HIV-1 binding and entry...
  63. pmc The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2
    Minsoo Kim
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 167:1241-53. 2004
    ..Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands...
  64. ncbi Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1
    Omar D Perez
    Department of Microbiology and Immunology, and The Baxter Laboratory of Genetic Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nat Immunol 4:1083-92. 2003
    ..LFA-1 stimulation lowered the threshold of T cell activation. Thus, LFA-1 signaling contributes to T cell activation and effects T cell differentiation...
  65. pmc Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily
    R S Larson
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
    J Cell Biol 108:703-12. 1989
    ..These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains...
  66. pmc HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse
    Clare Jolly
    The Sir William Dunn School of Pathology, University of Oxford, UK
    J Exp Med 199:283-93. 2004
    ..We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell...
  67. ncbi The involvement of lipid rafts in the regulation of integrin function
    Birgit Leitinger
    Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
    J Cell Sci 115:963-72. 2002
    ..The presence of integrin in lipid rafts under stimulating conditions that activate these receptors strongly indicates that the rafts have a key role in positively regulating integrin activity...
  68. pmc Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin
    A Qu
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 92:10277-81. 1995
    ....
  69. pmc Polarized localization of epithelial CXCL11 in chronic obstructive pulmonary disease and mechanisms of T cell egression
    Joanna C Porter
    Medical Research Council Laboratory of Molecular Cell Biology, University College London, London, UK
    J Immunol 180:1866-77. 2008
    ..This study highlights the role of the respiratory epithelium in the trafficking of T lymphocytes from the pulmonary interstitium and into the large airways, during the onset and resolution of pulmonary inflammation...
  70. pmc CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells
    Xi Chen
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 103:10346-51. 2006
    ..Thus, in YTS cells, a CD28 signal is used to polarize the MTOC and cytolytic granules to the NK cell immune synapse by stimulating sustained ERK2 activation...
  71. ncbi Effects of IL-8, Gro-alpha, and LTB(4) on the adhesive kinetics of LFA-1 and Mac-1 on human neutrophils
    S M Seo
    Institute of Biosciences and Bioengineering, Rice University, Houston 77005, USA
    Am J Physiol Cell Physiol 281:C1568-78. 2001
    ..These kinetic and topographical differences may indicate distinct functional contributions of LFA-1 and Mac-1 on neutrophils...
  72. pmc Rap1 functions as a key regulator of T-cell and antigen-presenting cell interactions and modulates T-cell responses
    Koko Katagiri
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Mol Cell Biol 22:1001-15. 2002
    ..Moreover, constitutive Rap1 activation rendered T cells unresponsive with accumulation of p27(Kip1). Our study indicates that the activation state of Rap1 has a decisive effect on the T-cell response to antigen...
  73. ncbi T cell receptor signaling precedes immunological synapse formation
    Kyeong Hee Lee
    Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, Saint Louis, MO 63110, USA
    Science 295:1539-42. 2002
    ..These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation...
  74. ncbi The role of the integrin LFA-1 in T-lymphocyte migration
    Andrew Smith
    Leukocyte Adhesion Laboratory, Cancer Research UK, London Research Institute, London, UK
    Immunol Rev 218:135-46. 2007
    ....
  75. ncbi Epitope mapping of antibodies to the C-terminal region of the integrin beta 2 subunit reveals regions that become exposed upon receptor activation
    C Lu
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 166:5629-37. 2001
    ..We thus define five different beta(2) stalk subregions, mAb binding to which correlates with effect on activation, and define regions in an interface that becomes exposed upon integrin activation...
  76. 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...
  77. ncbi Crucial importance of PKC-beta(I) in LFA-1-mediated locomotion of activated T cells
    Y Volkov
    Dublin Molecular Medicine Centre, Trinity College, Dublin 8, Ireland
    Nat Immunol 2:508-14. 2001
    ..These observations may have physiological equivalents at advanced (post-integrin activation) stages of lymphocyte extravasation...
  78. ncbi Coupling of the TCR to integrin activation by Slap-130/Fyb
    E J Peterson
    The Abramson Family Cancer Research Institute, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
    Science 293:2263-5. 2001
    ..These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals...
  79. pmc Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes
    D F Kucik
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Clin Invest 97:2139-44. 1996
    ..Cytochalasin D led to an equivalent increase in mobility and, at low doses, stimulated adhesion, implying that the nonadhesive state of LFA-1 is actively maintained by the lymphocyte cytoskeleton...
  80. ncbi Unidirectional budding of HIV-1 at the site of cell-to-cell contact is associated with co-polarization of intercellular adhesion molecules and HIV-1 viral matrix protein
    S Fais
    Institute of Virology, La Sapienza University, Rome, Italy
    AIDS 9:329-35. 1995
    ..To explore the possibility that HIV-1 budding and cellular adhesion molecules co-polarize at cell-to-cell contact sites. To investigate the incorporation of host-cell-derived adhesion molecules into HIV-1...
  81. ncbi Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics
    J M Faint
    University of Birmingham/Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom
    J Immunol 167:212-20. 2001
    ..In accord with this, CD45RA(+) memory cells were significantly underrepresented in lymph nodes, but account for virtually all CD8(+)CD45RA(+) T cells in peripheral tissues of the same individuals...
  82. ncbi Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b
    Wenying Zhang
    La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 278:23978-83. 2003
    ..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells...
  83. ncbi The functional interaction of the beta 2 integrin lymphocyte function-associated antigen-1 with junctional adhesion molecule-A is mediated by the I domain
    Line Fraemohs
    Department of Molecular Cardiovascular Research, Rheinisch Westfalische Technische Hochschule, University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
    J Immunol 173:6259-64. 2004
    ..Solid-phase binding assays confirmed a direct interaction of recombinant JAM-A with the immobilized locked-open I domain. These data provide the first evidence that the I domain of LFA-1 contains a functional binding site for JAM-A...
  84. pmc Integrin-dependence of lymphocyte entry into the splenic white pulp
    Charles G Lo
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
    J Exp Med 197:353-61. 2003
    ..These observations suggest that chemokine receptor signaling and the integrins LFA-1 and alpha 4 beta 1 function together to promote lymphocyte transit from the marginal zone into white pulp cords...
  85. ncbi A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation
    F Vincenti
    Transplant Service, University of California, San Francisco, CA, USA
    Am J Transplant 7:1770-7. 2007
    ..The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation...
  86. ncbi Activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage
    Lisa Dreolini
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3
    Biochem Biophys Res Commun 356:207-12. 2007
    ..Thus, activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage...
  87. ncbi Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice
    D P Andrew
    Amgen Inc, Boulder, USA
    Eur J Immunol 28:1959-69. 1998
    ..Finally, whereas anti-CD31 mAb blocked WT monocyte and neutrophil transendothelial cell migration they did not block LFA-1-deficient monocyte and neutrophil transendothelial migration...
  88. ncbi Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules
    C G Gahmberg
    Department of Biosciences, University of Helsinki, Finland
    Curr Opin Cell Biol 9:643-50. 1997
    ..Furthermore, much progress has been made in the study of integrin activation and the role of leukocyte adhesion molecules in disease...
  89. ncbi The importance of virus-associated host ICAM-1 in human immunodeficiency virus type 1 dissemination depends on the cellular context
    Salim Bounou
    Research Center in Infectious Diseases, CHUL Research Center, and Faculty of Medicine, Laval University, Quebec, Canada
    FASEB J 18:1294-6. 2004
    ..Altogether these data underscore the complexity of factors participating in virus-cell contact and efficient dissemination of HIV-1 to target cells...
  90. ncbi RTX toxins recognize a beta2 integrin on the surface of human target cells
    E T Lally
    Leon Levy Research Center for Oral Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6002, USA
    J Biol Chem 272:30463-9. 1997
    ..These experiments identify LFA-1 as a cell surface receptor that mediates toxicity of members of this family of pore-forming toxins...
  91. ncbi Cloning and expression of the chicken CD18 cDNA
    C A Bilsland
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115
    J Leukoc Biol 55:501-6. 1994
    ..The chicken beta 2 can associate on the cell surface with the human alpha subunit of LFA-1 and yields a hybrid molecule capable of binding to purified ICAM-1 and ICAM-3...
  92. ncbi Leukocyte-epithelial interactions
    Ke Zen
    Division of Gastrointestinal Pathology, Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Boulevard, Room 1053, 615 Michael Street, Atlanta, GA 30322, USA
    Curr Opin Cell Biol 15:557-64. 2003
    ....
  93. ncbi Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human lymph nodes
    H Tanaka
    Institute of Medical Science, Jikei University School of Medicine, Tokyo, Japan
    Pathol Int 44:268-79. 1994
    ..Furthermore, both LFA-1- and VLA4-positive lymphocytes localized around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways play an important role in the lymphocyte recognition of antigen-presenting cells...
  94. ncbi The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus
    D E Staunton
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115
    Cell 61:243-54. 1990
    ..Our analysis suggests that rhinoviruses mimic LFA-1 in binding to the most membrane-distal, and thus most accessible, site of ICAM-1...
  95. pmc ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation
    Hongyan Wang
    Molecular Immunology Section, Department of Immunology, Imperial College London, Hammersmith Campus, London W12 ONN, England, UK
    J Exp Med 200:1063-74. 2004
    ..Our findings identify ADAP-SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production...
  96. pmc Stimulation of naïve T-cell adhesion and immunological synapse formation by chemokine-dependent and -independent mechanisms
    Shannon K Bromley
    Graduate Program in Immunology, Washington University School of Medicine, St Louis, MO, USA
    Immunology 106:289-98. 2002
    ..However, basal and antigen-stimulated T-cell adhesion to dendritic cells was not sensitive to pertussis toxin. Thus, there are chemokine-independent mechanisms that initiate adhesion between T cells and dendritic cells...
  97. pmc LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice
    H Lu
    Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Clin Invest 99:1340-50. 1997
    ..Our results demonstrate that Mac-1 plays a critical role in mediating binding of neutrophils to fibrinogen and neutrophil degranulation, but is not necessary for effective neutrophil emigration, which is more dependent upon LFA-1...
  98. ncbi Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L
    Makiko Kumagai-Braesch
    Department of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
    Transplantation 83:1259-67. 2007
    ..The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C57BL/6 mice with streptozotocin-induced diabetes...
  99. ncbi Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes
    Susanna Fagerholm
    Department of Biosciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland
    Eur J Immunol 32:1670-8. 2002
    ..Retransfection of human Lck in JCaM1.6 cells restored adhesion. Thus, Lck is involved in regulating CD11a/CD18-integrins in T cells...
  100. pmc Cell adhesion molecule distribution relative to neutrophil surface topography assessed by TIRFM
    Sandrine A Hocdé
    Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
    Biophys J 97:379-87. 2009
    ..The results confirm differences among adhesion molecules in their surface distribution and reveal how the availability of specific adhesion molecules is altered by mechanical compression of the surface in live cells...
  101. ncbi Talin1 regulates TCR-mediated LFA-1 function
    William T N Simonson
    Program in Cellular and Molecular Biology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA
    J Immunol 177:7707-14. 2006
    ..Together, our findings indicate that TCR-induced up-regulation of LFA-1-dependent adhesiveness and resulting T cell-APC conjugation require talin1...

Research Grants50

  1. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
    ....
  2. LFA-1 in Lymphocyte Migration
    Minsoo Kim; Fiscal Year: 2013
    ..Thus, the molecular and cellular characterization of LFA-1 activation during T cell migration in vivo will enhance development of new therapeutics. ..
  3. Migration of polyomavirus JC across the blood-brain-barrier
    Vivek Nerurkar; Fiscal Year: 2009
    ....
  4. LYMPHOCYTE FUNCTION ASSOCIATED ANTIGENS
    Timothy A Springer; Fiscal Year: 2013
    ..The molecular characterizationof LFA-1 and its antagonists proposed in this grant will enhance development of new drugs. ..
  5. Protein-mediated molecular adhesion: AFM studies
    VINCENT MOY; Fiscal Year: 2006
    ..abstract_text> ..
  6. Integrin LFA-1 antagonists
    Motomu Shimaoka; Fiscal Year: 2009
    ..The active LFA-1-selective mAbs will be used for blocking ligand binding as well as probing the active LFA-1 on the cell surface in leukocyte migration and formation of immunological synapse. ..
  7. UCSD Hillcrest Flow Cytometer
    Paul Mills; Fiscal Year: 2003
    ..It will also be the centerpiece for an environment of shared ideas and collaboration among investigators who now utilize cytometry for their research. ..
  8. SYMPATHETIC NERVOUS SYSTEM REGULATION OF CELL ADHESION
    Paul J Mills; Fiscal Year: 2010
    ..abstract_text> ..
  9. Chemokine Receptor Chimeras by Synthetic Gene Library
    Michael Dustin; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  10. Inverted two photon laser scanning microscope for host defense
    Michael Dustin; Fiscal Year: 2008
    ..The impact on public health will be to develop better strategies to fight infections and reduce the incidence of pathogen triggered autoimmunity. [unreadable] [unreadable] [unreadable]..
  11. SIGNAL TRANSDUCTION IN SENSITIZED AIRWAY SMOOTH MUSCLE
    Michael Grunstein; Fiscal Year: 2002
    ....
  12. Immunoreceptors
    Michael Dustin; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  13. Virus-Induced Mechanics of Altered Airway Responsiveness
    Michael Grunstein; Fiscal Year: 2008
    ..It is anticipated that the findings from these proposed studies would yield important new insights into the mechanistic interplay between viral respiratory pathogens, atopy, and altered airway responsiveness. [unreadable] [unreadable]..
  14. Maturation of Non-Specific Airways Reactivity
    Michael Grunstein; Fiscal Year: 2007
    ....
  15. Actinobacillus actinomycetemcomitans Leukotoxin Induced Cell Death
    Edward Lally; Fiscal Year: 2007
    ..abstract_text> ..
  16. Diagnosis and Pathogenesis of Early Lyme Disease
    Allen Steere; Fiscal Year: 2007
    ..In addition, greater knowledge of spirochetal virulence and host factors associated with severe disease may allow the development of laboratory markers for patients who would benefit from more intensive treatment. ..
  17. Environmental effects on lupus T cell DNA methylation and gene expression
    Bruce Richardson; Fiscal Year: 2009
    ..Evidence that dietary modification can ameliorate aberrant gene expression in vitro and disease severity in the murine model will lead to studies extending these results to lupus patients. ..
  18. Immune cell dynamics during central nervous system viral infection
    JUAN DE LA TORRE; Fiscal Year: 2008
    ..abstract_text> ..
  19. Aberrant gene expression in CD4+CD28-T cells: mechanisms
    Bruce C Richardson; Fiscal Year: 2010
    ..These studies will identify mechanisms modifying gene expression in this pathologic subset, and suggest ways to restore normal gene expression in these cells. ..
  20. DIFFUSION MRI AS BIOMARKER FOR THERAPY RESPONSE IN BREAST CANCER METASTASES
    Alison T Stopeck; Fiscal Year: 2010
    ....
  21. MONOCYTE ADHESION TO ATHEROMA IN GENE TARGETED MICE
    Klaus Ley; Fiscal Year: 2009
    ..The proposed work may enable the design of interventions into the chemokine network to stabilize atherosclerotic plaques by reducing their content of inflammatory cells. ..
  22. LYME ARTHRITIS: A NEW EPIDEMIC DISEASE
    Allen C Steere; Fiscal Year: 2010
    ..Furthermore, this work brings us closer to the long-term goal of direct comparisons of antigens in Lyme arthritis and rheumatoid arthritis synovia. ..
  23. Advancing High Throughput Flow Cytometry
    Bruce S Edwards; Fiscal Year: 2010
    ....
  24. MECHANISMS OF INFLAMMATORY LIVER INJURY
    C Smith; Fiscal Year: 2001
    ..Specific Aim 4 will define the potential sources and function of soluble ICAM-1 in inflammatory liver injury. ..
  25. EXTRAVASCULAR TRAFFICKING OF HIV+ CELLS AND PROGNOSIS
    Holly Birdsall; Fiscal Year: 2003
    ....
  26. RISK OF PORCINE PICORNAVIRUS IN XENOTRANSPLATATION
    M Njenga; Fiscal Year: 2003
    ..The long-term goal is to transplant pig organs/tissues containing persistent porcine virus into primates in order to determine the risk of disease. ..
  27. GENDER-SPECIFIC T CELL HOMING AND AUTOIMMUNITY
    Bruce Richardson; Fiscal Year: 2003
    ..Dr. Richardson anticipates that these studies will identify novel and important mechanisms contributing to the increased incidence and severity of autoimmune disease in women. ..
  28. INDUCTION OF SPECIFIC IMMUNE TOLERANCE
    TERRY POTTER; Fiscal Year: 2003
    ..In the current application, it is proposed to examine the function and activity of the CD8 targeting hAb in animal models of organ transplantation. ..
  29. Frequency and Function of HIV-specific T-cells in GALT
    Barbara Shacklett; Fiscal Year: 2003
    ..We will also test alternate hypotheses to explain the apparent low levels of perforin expression in GALT. ..
  30. SELECTIN MEDIATED LEUKOCYTE ADHESION IN VIVO
    Klaus Ley; Fiscal Year: 2002
    ..The knowledge gained will improve the understanding of the inflammatory process and provide significant information pertinent to the development of potential anti-inflammatory therapies for future clinical use in patients. ..
  31. Molecular Mechanisms That Regulate CD11d Expression
    JOHN NOTI; Fiscal Year: 2004
    ..Transgenic analysis of the CD11d cis elements will be done to complement these studies. These studies will expand our understanding of normal myeloid development and leukemogenesis. ..
  32. Baltimore VIRAHEP-C Clinical Center
    Charles Howell; Fiscal Year: 2005
    ..These studies may provide important new insights into the pathogenesis of HCV and lead to novel therapies for chronic HCV. ..
  33. BIOMECHANICS OF LEUKOCYTE ADHESION MOLECULES
    Klaus Ley; Fiscal Year: 2002
    ..Milestones for the following years are listed in the timeline. ..
  34. T cell Interactions in the CNS During Viral Persistence
    Dorian McGavern; Fiscal Year: 2005
    ..The main objective of this research is to define the immunologic parameters that contribute to viral clearance versus persistence in the CNS and foster approaches that tip the balance in favor of clearance. ..
  35. SIGNIFICANCE OF AGE DEPENDENT CHANGES IN DNA METHYLATION
    Bruce Richardson; Fiscal Year: 2002
    ..This approach may also prove useful in characterizing genes that have altered expression with aging in lymphocytes and other cell types, and that may contribute to the development of autoimmunity and malignancies in the elderly. ..
  36. In Situ Analysis of Hepatitis B virus-specific T cells
    Dorian McGavern; Fiscal Year: 2006
    ..The main objective of this research is to more precisely define the contribution of HBV-specific CTL to viral clearance and pathogenesis by providing the first comprehensive analysis of these cells in situ. ..
  37. Assay for Formylpeptide Receptor Family Ligands(RMI)
    Bruce Edwards; Fiscal Year: 2005
    ..We expect that such compounds will prove to be important tools with which to advance the understanding and therapy of inflammation-associated diseases. ..
  38. LISTERIA PROTEINS EFFECTS ON CELL FUNCTION
    TERRY POTTER; Fiscal Year: 2001
    ..These experiments should provide valuable information on the interaction of LM with phagocytic cells and may provide insights into the phagocytosis and killing of other intracellular bacteria. ..
  39. Dynamic Strenghts of Leukoctye Adhesion Bonds
    Evan A Evans; Fiscal Year: 2011
    ..abstract_text> ..
  40. Neutralizing Compounds for Viral Hemorrhagic Fever
    Richard Larson; Fiscal Year: 2005
    ....
  41. Neutralizing Compounds for Viral Hemorrhagic Fever
    Richard Larson; Fiscal Year: 2003
    ..abstract_text> ..
  42. Antigen Presentation in CD4-mediated Cardiac Rejection
    Todd Grazia; Fiscal Year: 2003
    ..endothelial cells). These chimeric mice can then serve as heart donors into immunodeficient recipients reconstituted with CD4 T-cells. Results of these studies will have significant implications for targeted therapy. ..
  43. Microenvironmental mechanisms of leukemia cell survival
    Richard Larson; Fiscal Year: 2009
    ..In addition, we will share this data with Dr. Tom Look at the Dana Farber Cancer Center in order to correlate his genetic findings in his T-ALL Zebra fish model with our human studies. ..
  44. Multiplex Screening for ABC Transporter Inhibitors
    Richard Larson; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  45. Leukocyte Mechanotransduction of Fluid Shear Stress
    HAINSWORTH SHIN; Fiscal Year: 2006
    ..These studies will elucidate a possible control mechanism which, in the absence of ' agonists, prevents leukocyte pseudopod formation and migration under physiological conditions. [unreadable] [unreadable]..
  46. Effect of Statins on HIV-1 Biology
    CRAIG FLETCHER; Fiscal Year: 2007
    ..abstract_text> ..
  47. CXCR3 in Liver Lymphocyte Trafficking in GVHD Hepatitis
    Tohru Sato; Fiscal Year: 2006
    ..By using the methods established from my studies of CXCR6, I plan to characterize the role of CXCR3 and its interplay with CXCR6 as liver homing molecules and possible therapeutic targets. ..
  48. Leukotoxin production by A. actinomycetemcomitans
    SCOTT KACHLANY; Fiscal Year: 2009
    ..This new information may lead to the design of therapeutic agents that can disrupt leukotoxin activity and ultimately treat or prevent disease. ..