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Molecular analysis of the physiological and pathophysiological role of α4-integrins

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Abbreviations

VCAM-1 :

Vascular cell adhesion molecule-1

ICAM :

Intercellular adhesion molecule

MAdCAM-1 :

Mucosal addressin cell adhesion molecule

TCR :

T cell receptor for antigen

MIP :

Macrophage inflammatory protein

LFA :

Lymphocyte function associated antigen

mAb :

Monoclonal antibody

References

  1. Lobb RR, Hemler ME (1994) The pathophysiologic role of α4 integrins in vivo. J Clin Invest 94:1722–1728

    Google Scholar 

  2. Bevilacqua MP (1993) Endothelial leukocyte adhesion molecules. Annu Rev Immunol 11:767–804

    Google Scholar 

  3. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Article  CAS  PubMed  Google Scholar 

  4. Postigo AA, Teixido J, Sanchez Madrid F (1993) The α4β1/VCAM-1 adhesion pathway in physiology and disease. Res Immunol 144:723–735

    Google Scholar 

  5. Issekutz TB (1993) The contributions of integrins to leukocyte infiltration in inflamed tissues. Curr Top Microbiol Immunol 184:177–185

    Google Scholar 

  6. Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84:2068–2101

    Google Scholar 

  7. Loftus JC, Smith JW, Ginsberg MH (1994) Integrin-mediated cell adhesion: the extracellular face. J Biol Chem 269:25235–25238

    Google Scholar 

  8. Ruoslahti E, Reed JC (1994) Anchorage dependence, integrins, and apoptosis. Cell 77:477–478

    Google Scholar 

  9. Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25

    Article  CAS  PubMed  Google Scholar 

  10. Hemler ME, Elices MJ, Parker C, Takada Y (1990) Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions. Immunol Rev 114:45–65

    Google Scholar 

  11. Teixido J, Parker CM, Kassner PD, Hemler ME (1992) Functional and structural analysis of VLA-4 integrin α4 subunit cleavage. J Biol Chem 267:1786–1791

    Google Scholar 

  12. Wayner EA, Garcia Pardo A, Humphries MJ, McDonald JA, Carter WG (1989) Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol 109:1321–1330

    Google Scholar 

  13. McIntyre BW, Evans EL, Bednarczyk JL (1989) Lymphocyte surface antigen L25 is a member of the integrin receptor superfamily. J Biol Chem 264:13745–13750

    Google Scholar 

  14. Sanchez Madrid F, De Landazuri MO, Morago G, Cebrian M, Acevedo A, Bernabeu C (1986) VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol 16:1343–1349

    Google Scholar 

  15. Parker CM, Pujades C, Brenner MB, Hemler ME (1993) α4/180, a novel form of the integrin α4 subunit. J Cell Biol 268:7028–7035

    Google Scholar 

  16. Postigo AA, Sanchez Mateos P, Lazarovits AI, Sanchez Madrid F, De Landazuri MO (1993) α4β7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1: expression and function of α4 integrins on human B lymphocytes. J Immunol 151:2471–2483

    Google Scholar 

  17. Schweighoffer T, Tanaka Y, Tidswell M, Erle DJ, Horgan KJ, Ginther Luce GE, Lazarovits AI, Buck D, Shaw S (1993) Selective expression of integrin α4β7 on a subset of human CD4+ memory T cells with hallmarks of gut-tropism. J Immunol 151:717–729

    Google Scholar 

  18. Erle DJ, Briskin MJ, Butcher EC, Garcia Pardo A, Lazarovits AI, Tidswell M (1994) Expression and function of the MAdCAM-1 receptor, integrin α4β7, on human leukocytes. J Immunol 153:517–528

    Google Scholar 

  19. Shimizu Y, van Seventer GA, Horgan KJ, Shaw S (1990) Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature 345:250–253

    Google Scholar 

  20. Picker LJ, Treer JR, Nguyen M, Terstappen LWMM, Hogg N, Yednock T (1993) Coordinate expression of β1 and β2 integrin “activation” epitopes during T cell responses in secondary lymphoid tissue. Eur J Immunol 23:2751–2757

    Google Scholar 

  21. Tiisala S, Paavonen T, Renkonen R (1995) αEβ7 and α4β7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages. Eur J Immunol 25:411–417

    Google Scholar 

  22. Rosen GD, Sanes JR, LaChance R, Cunningham JM, Roman J, Dean DC (1992) Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell 69:1107–1119

    Article  CAS  PubMed  Google Scholar 

  23. Sheppard AM, Onken MD, Rosen GD, Noakes PG, Dean DC (1994) Expanding roles for α4 integrins and its ligands in development. Cell Adhes Commun 2:27–43

    Google Scholar 

  24. Nojima Y, Humphries MJ, Mould AP, Komoriya A, Yamada KM, Schlossman SF, Morimoto C (1990) VLA-4 mediates CD3-dependent CD4+ T cell activation via the CS1 alternatively spliced domain of fibronectin. J Exp Med 172:1185–1192

    Google Scholar 

  25. Mould AP, Wheldon LA, Komoriya A, Wayner EA, Yamada KM, Humphries MJ (1990) Affinity Chromatographic isolation of the melanoma adhesion receptor for the IIICS region of fibronectin and its identification as the integrin α4β1. J Biol Chem 265:4020–4024

    Google Scholar 

  26. Mould AP, Komoriya A, Yamada KM, Humphries MJ (1991) The CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin α4β1. Inhibition of α4β1 function by RGD peptide homologues. J Biol Chem 266:3579–3585

    Google Scholar 

  27. Komoriya A, Green LJ, Mervic M, Yamada SS, Yamada KM, Humphries MJ (1991) The minimal essential sequence for a major cell type-specific adhesion site (CS1) within the alternatively spliced type III connecting segment domain of fibronectin is leucine-aspartic acid-valine. J Biol Chem 266:15075–15079

    Google Scholar 

  28. Mould AP, Humphries MJ (1991) Identification of a novel recognition sequence for the integrin α4β1 in the COOH-terminal heparin-binding domain of fibronectin. EMBO J 10:4089–4095

    Google Scholar 

  29. Sanchez Aparicio P, Dominguez Jimenez C, Garcia Pardo A (1994) Activation of the α4β1 integrin through the β1 subunit induces recognition of the RGDS sequence in fibronectin. J Cell Biol 126:271–279

    Google Scholar 

  30. Ruegg C, Postigo AA, Sikorski EE, Butcher EC, Pytela R, Erle DJ (1992) Role of integrin α4β7/α4βp in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. J Cell Biol 117:179–189

    Google Scholar 

  31. Strauch UG, Lifka A, Gosslar U, Kilshaw PJ, Clements J, Holzmann B (1994) Distinct binding specificities of integrins α4β7 (LPAM-1), α4β1 (VLA-4), and αIELβ7. Int Immunol 6:263–275

    Google Scholar 

  32. Yabkowitz R, Dixit VM, Guo N, Roberts DD, Shimizu Y (1993) Activated T cell adhesion to thrombospondin is mediated by the α4β1 (VLA-4) and α5β1 (VLA-5) integrins. J Immunol 151:149–158

    Google Scholar 

  33. Mosher DF (1990) Physiology of thrombospondin. Annu Rev Med 41:85–97

    Google Scholar 

  34. Ennis E, Isberg RR, Shimizu Y (1993) Very late antigen 4-dependent adhesion and costimulation of resting human T cells by the bacterial β1 integrin ligand invasin. J Exp Med 177:207–212

    Google Scholar 

  35. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60:577–584

    Google Scholar 

  36. Osborn L, Vassallo C, Benjamin CD (1992) Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule 1. J Exp Med 176:99–107

    Google Scholar 

  37. Vonderheide RH, Springer TA (1992) Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional α4 integrin counter-receptor on stimulated endothelium. J Exp Med 175:1433–1442

    Google Scholar 

  38. Kilger G, Needham LA, Nielsen PJ, Clements J, Vestweber D, Holzmann B (1995) Differential regulation of α4 integrin-dependent binding to domains 1 and 4 of vascular cell adhesion molecule-1. J Biol Chem 270:5979–5984

    Google Scholar 

  39. Needham LA, van Dijk S, Pigott R, Edwards M, Shepherd M, Hemingway I, Jack L, Clements J (1994) Activation dependent and independent VLAA-4 binding sites on vascular adhesion molecule-1. Cell Adhes Commun 2:87–99

    Google Scholar 

  40. Osborn L, Vassallo C, Griffiths Browning B, Tizard R, Haskard DO, Benjamin CD, Dougas I, Kirchhausen T (1994) Arrangement of domains and amino acid residues required for binding of vascular adhesion molecule-1 to its counter-receptor VLA-4 (α4β1). J Cell Biol 124:601–608

    Google Scholar 

  41. Renz ME, Chiu HH, Jones S, Fox J, Kim KJ, Presta LG, Fong S (1994) Structural requirements for adhesion of soluble recombinant murine vascular cell adhesion molecule-1 to α4β1. J Cell Biol 125:1395–1406

    Google Scholar 

  42. Vonderheide RH, Tedder TF, Springer TA, Staunton DE (1994) Residues within a conserved amino acid motif of domains 1 and 4 of VCAM-1 are required for binding to VLA-4. J Cell Biol 125:215–222

    Google Scholar 

  43. Clements JM, Newham P, Shepherd M, Gilbert R, Dudgeon TJ, Needham LA, Edwards M, Berry L, Brass A, Humphries MJ (1994) Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV site in fibronectin. J Cell Sci 107:2127–2135

    Google Scholar 

  44. Streeter PR, Berg EL, Rouse BT, Bargatze RF, Butcher EC (1988) A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature 331:41–46

    Google Scholar 

  45. Briskin MJ, McEvoy LM, Butcher EC (1993) MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1. Nature 363:461–464

    Google Scholar 

  46. Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, Weissman IL, Hamann A, Butcher EC (1993) α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74:185–195

    Google Scholar 

  47. Tanaka Y, Albelda SM, Horgan KJ, van Seventer GA, Shimizu Y, Newman W, Hallam J, Newman PJ, Buck CA, Shaw S (1992) CD31 expressed on distinctive T cell subsets is a preferential amplifier of β1 integrin-mediated adhesion. J Exp Med 176:245–253

    Google Scholar 

  48. Tanaka Y, Adams DH, Hubscher S, Hirano H, Siebenlist U, Shaw S (1993) T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1β. Nature 361:79–82

    Google Scholar 

  49. Rubinstein E, Le Naour F, Billard M, Prenant M, Boucheix C (1994) CD9 antigen is an accessory subunit of the VLA integrin complex. Eur J Immunol 24:3005–3013

    Google Scholar 

  50. Masellis Smith A, Shaw ARE (1994) CD9-regulated adhesion: anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. J Immunol 152:2768–2777

    Google Scholar 

  51. Masumoto A, Hemler ME (1993) Mutation of putative divalent cation sites in the α4 subunit of the integrin VLA-4: distinct effects on adhesion to CS1/fibronectin, VCAM-1, and invasin. J Cell Biol 123:245–253

    Google Scholar 

  52. Masumoto A, Hemler ME (1993) Multiple activation states of VLA-4: mechanistic differences between adhesion to CSl/fibronectin and to vascular cell adhesion molecule-1. J Biol Chem 268:228–234

    Google Scholar 

  53. Kassner PD, Hemler ME (1993) Interchangeable a chain cytoplasmic domains play a positive role in control of cell adhesion mediated by VLA-4, a β1 integrin. J Exp Med 178:649–660

    Google Scholar 

  54. Crowe DT, Chiu H, Fong S, Weissman IL (1994) Regulation of the avidity of integrin α4β7 by the β7 cytoplasmic domain. J Biol Chem 269:14411–14418

    Google Scholar 

  55. Kassner PD, Kawaguchi S, Hemler ME (1994) Minimum α chain cytoplasmic tail sequences needed to support integrin-mediated adhesion. J Biol Chem 269:19859–19867

    Google Scholar 

  56. Hahne M, Wenger RH, Vestweber D, Nielsen PJ (1994) The heat stable antigen can alter very late antigen 4-mediated adhesion. J Exp Med 179:1391–1395

    Google Scholar 

  57. Nojima Y, Rothstein DM, Sugita K, Schlossman SF, Morimoto C (1992) Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. J Exp Med 175:1045–1053

    Google Scholar 

  58. Freedman AS, Rhynhart K, Nojima Y, Svahn J, Eliseo L, Benjamin CD, Morimoto C, Vivier E (1993) Stimulation of protein tyrosine phosphorylation in human B cells after ligation of the β1 integrin VLA-4. J Immunol 150:1645–1652

    Google Scholar 

  59. Yurochko AD, Liu DY, Eierman D, Haskill S (1992) Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction. Proc Natl Acad Sci U S A 89:9034–9038

    Google Scholar 

  60. Romanic AM, Madri JA (1994) The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells is VCAM-1dependent. J Cell Biol 125:1165–1178

    Google Scholar 

  61. Janeway CA Jr., Bottomly K (1994) Signals and signs for lymphocyte responses. Cell 76:275–285

    Google Scholar 

  62. van Seventer GA, Newman W, Shimizu Y, Nutman TB, Tanaka Y, Horgan KJ, Gopal TV, Ennis E, O'Sullivan D, Grey H, Shaw S (1991) Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med 174:901–913

    Google Scholar 

  63. Damle NK, Aruffo A (1991) Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+ T lymphocytes. Proc Natl Acad Sci U S A 88:6403–6407

    Google Scholar 

  64. Burkly LC, Jakubowski A, Newman BM, Rosa MD, Chi Rosso G, Lobb RR (1991) Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation. Eur J Immunol 21:2871–2875

    Google Scholar 

  65. Damle NK, Klussman K, Leytze G, Myrdal S, Aruffo A, Ledbetter JA, Linsley PS(1994) Costimulation of T lymphocytes with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 induces functional expression of CTLA-4, a second ligand for B7. J Immunol 152:2686–2697

    Google Scholar 

  66. Damle NK, Klussman K, Leytze G, Aruffo A, Linsley PS, Ledbetter JA (1993) Costimulation with integrin ligands intercellular adhesion molecule-1 or vascular adhesion molecule-1 augments activation-induced death of antigen-specific CD4+ T lymphocytes. J Immunol 151:2368–2379

    Google Scholar 

  67. Freedman AS, Munro JM, Rice GE, Bevilacqua MP, Morimoto C, McIntyre BW, Rhynhart K, Pober JS, Nadler LM (1990) Adhesion of human B cells to germinal centers in vitro involves VLA-4 and INCAM-110. Science 249:1030–1033

    Google Scholar 

  68. Koopman G, Parmentier HK, Schuurman HJ, Newman W, Meijer CJ, Pals ST (1991) Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways. J Exp Med 173:1297–1304

    Google Scholar 

  69. Koopman G, Keehnen RM, Lindhout E, Newman W, Shimizu Y, van Seventer GA, de Groot C, Pals ST (1994) Adhesion through the LFA-1 (CD11a/CD18)-ICAM-l (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. J Immunol 152:3760–3767

    Google Scholar 

  70. Miyake K, Medina K, Ishihara K, Kimoto M, Auerbach R, Kincade PW (1991) A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J Cell Biol 114:557–565

    Google Scholar 

  71. Miyake K, Weissman IL, Greenberger JS, Kincade PW (1991) Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis. J Exp Med 173:599–607

    Google Scholar 

  72. Kerst MJ, Sanders JB, Slaper Cortenbach ICM, Doorakkers MC, Hooibrink B, van Oers RHJ, von dem Borne AEGK, van der School CE (1993) α4β1 and α5β1 are differentially expressed during myelopoiesis and mediate the adherence of human CD34+ cells to fibronectin in an activation-dependent way. Blood 81:344–351

    Google Scholar 

  73. Liesveld JL, Winslow JM, Frediani KE, Ryan DH, Abboud CN (1993) Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Blood 81:112–121

    Google Scholar 

  74. Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok Storb B, Gallatin WM (1992) Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 80:388–395

    Google Scholar 

  75. Teixido J, Hemler ME, Greenberger JS, Anklesaria P (1992) Role of β1 and β2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma. J Clin Invest 90:358–367

    Google Scholar 

  76. Ryan DH, Nuccie BL, Abboud CN, Winslow JM (1991) Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells. J Clin Invest 88:995–1004

    Google Scholar 

  77. Sadahira Y, Yoshino T, Monobe Y (1995) Very late activation antigen 4-vascular cell adhesion molecule 1 interaction is involved in the formation of erythroblastic islands. J Exp Med 181:411–415

    Google Scholar 

  78. Papayannopoulou T, Nakamoto B (1993) Peripheralization of hemopoietic progenitors in primates treated with anti-VLA-4 integrin. Proc Natl Acad Sci U S A 90:9374–9378

    Google Scholar 

  79. Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67:1033–1036

    Google Scholar 

  80. Shimizu Y, Newman W, Tanaka Y, Shaw S (1992) Lymphocyte interactions with endothelial cells. Immunol Today 13:106–112

    Google Scholar 

  81. Berlin C, Bargatze RF, Campbell JJ, von Andrian UH, Szabo MC, Hasslen SR, Nelson RD, Berg EL, Erlandsen SL, Butcher EC (1995) α4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80:413–422

    Google Scholar 

  82. Sriramarao P, von Andrian UH, Butcher EC, Bourdon MA, Broide DH (1994) L-selectin and very late antigen-4 integrin promote eosinophil rolling at physiological shear rates in vivo. J Immunol 153:4238–4246

    Google Scholar 

  83. Jones DA, McIntire LV, Smith CW, Picker LJ (1994) A two step adhesion cascade for T cell/endothelial interactions under flow conditions. J Clin Invest 94:2443–2450

    Google Scholar 

  84. Alon R, Kassner PD, Woldemar Carr M, Finger EB, Hemler ME, Springer TA (1995) The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 128:1243–1253

    Google Scholar 

  85. Meerschaert J, Furie MB (1994) Monocytes use either CD11/CD18 or VLA-4 to migrate across human endothelium in vitro. J Immunol 152:1915–1926

    Google Scholar 

  86. Chuluyan HE, Issekutz AC (1993) VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes. J Clin Invest 92:2768–2777

    Google Scholar 

  87. Chan PY, Aruffo A (1993) VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin. J Biol Chem 268:24655–24664

    Google Scholar 

  88. Chan BM, Kassner PD, Schiro JA, Byers HR, Kupper TS, Hemler ME (1992) Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains. Cell 68:1051–1060

    Google Scholar 

  89. Picker LJ, Butcher EC (1992) Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol 10:561–591

    Google Scholar 

  90. Picker LJ (1994) Control of lymphocyte homing. Curr Opin Immunol 6:394–406

    Google Scholar 

  91. Holzmann B, Weissman IL (1989) Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like α chain associated with either of two integrin β chains, one of which is novel. EMBO J 8:1735–1741

    Google Scholar 

  92. Holzmann B, McIntyre BW, Weissman IL (1989) Identification of a murine Peyer's patch-specific lymphocyte homing receptor as an integrin molecule with an α chain homologous to human VLA-4α. Cell 56:37–46

    Google Scholar 

  93. Hu MC, Crowe DT, Weissman IL, Holzmann B (1992) Cloning and expression of mouse integrin βp (β7): a functional role in Peyer's patch-specific lymphocyte homing. Proc Natl Acad Sci U S A 89:8254–8258

    Google Scholar 

  94. Issekutz TB (1991) Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo. J Immunol 147:4178–4184

    Google Scholar 

  95. Hamann A, Andrew DP, Jablonski Westlich D, Holzmann B, Butcher EC (1994) Role of α4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol 152:3282–3293

    Google Scholar 

  96. Andrew DP, Berlin C, Honda S, Yoshino T, Hamann A, Holzmann B, Kilshaw PJ, Butcher EC (1994) Distinct but overlapping epitopes are involved in α4β7-mediated adhesion to vascular cell adhesion molecule-1, mucosal addressin-1, fibronectin, and lymphocyte aggregation. J Immunol 153:3847–3861

    Google Scholar 

  97. Bell RG, Issekutz T (1993) Expression of a protective intestinal immune response can be inhibited at three distinct sites by treatment with anti-α4 integrin. J Immunol 151:4790–4802

    Google Scholar 

  98. Chisholm PL, Williams CA, Lobb RR (1993) Monoclonal antibodies to the integrin α4 subunit inhibit the murine contact hypersensitivity response. Eur J Immunol 23:682–688

    Google Scholar 

  99. Ferguson TA, Kupper TS (1993) Antigen-independent processes in antigen-specific immunity: a role for α4 integrin. J Immunol 150:1172–1182

    Google Scholar 

  100. Issekutz TB (1993) Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivityinduced inflammation. Am J Pathol 143:1286–1293

    Google Scholar 

  101. Ferguson TA, Mizutani H, Kupper TS (1991) Two integrinbinding peptides abrogate T cell-mediated immune responses in vivo. Proc Natl Acad Sci U S A 88:8072–8076

    Google Scholar 

  102. Isobe M, Suzuki JI, Yagita H, Okumura K, Yamazaki S, Nagai R, Yazaki Y, Sekiguchi M (1994) Immunosuppression to cardiac allografts and soluble antigens by anti-vascular cellular adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies. J Immunol 153:5810–5818

    Google Scholar 

  103. Winn RK, Harlan JM (1993) CD18-independent neutrophil and mononuclear leukocyte emigration into the peritoneum of rabbits. J Clin Invest 92:1168–1173

    Google Scholar 

  104. Yednock TA, Gannon C, Fritz LC, Sanchez Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin. Nature 356:63–66

    Google Scholar 

  105. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CAJ (1994) Surface expression of α4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177:57–68

    Google Scholar 

  106. Yang XD, Karin N, Tisch R, Steinman L, McDevitt HO (1993) Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen 4 adhesion receptors. Proc Natl Acad Sci U S A 90:10494–10498

    Google Scholar 

  107. Burkly LC, Jakubowski A, Hattori M (1994) Protection against adoptive transfer of autoimmune diseases mediated through very late antigen-4 integrin. Diabetes 43:529–534

    Google Scholar 

  108. Baron JL, Reich EP, Visintin I, Janeway CAJ (1994) The pathogenesis of adoptive murine autoimmune diabetes requires an interaction between α4-integrins and vascular cell adhesion molecule-1. J Clin Invest 93:1700–1708

    Google Scholar 

  109. Yang XD, Michie SA, Tisch R, Karin N, Steinman L, McDevitt HO (1994) A predominant role of intgrin α4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 91:12604–12608

    Google Scholar 

  110. Faveeuw C, Gagnerault MC, Lepault F (1994) Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. J Immunol 152:5969–5978

    Google Scholar 

  111. Hänninen A, Taylor C, Streeter PR, Stark LS, Sarte JM, Shizuru JA, Simell O, Michie SA (1993) Vascular addressins are induced on islets during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium. J Clin Invest 92:2590–2515

    Google Scholar 

  112. Molina A, Sanchez Madrid F, Brico T, Martin A, Barat A, Alvarez V, Mampaso F (1994) Prevention of mercuric chloride-induced nephritis in the brown norway rat by treatment with antibodies against the α4 integrin. J Immunol 153:2313–2320

    Google Scholar 

  113. Issekutz TB, Issekutz AC (1991) T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4. Clin Immunol Immunopathol 61:436–447

    Google Scholar 

  114. Issekutz AC, Issekutz TB (1995) Monocyte migration to arthritis in the rat utilizes both CD11/CD18 and very late activation antigen 4 integrin mechanisms. J Exp Med 181:1197–1203

    Google Scholar 

  115. Lazarovits AI, Karsh J (1993) Differential expression in rheumatoid synovium and synovial fluid of α4β7 integrin: a novel receptor for fibronectin and vascular cell adhesion molecule-1. J Immunol 151:6482–6489

    Google Scholar 

  116. Laffon A, Garcia Vicuna R, Humbria A, Postigo AA, Corbi AL, De Landazuri MO, Sanchez Madrid F (1991) Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis. J Clin Invest 88:546–552

    Google Scholar 

  117. Podolsky DK, Lobb R, King N, Benjamin CD, Pepinsky B, Sehgal P, de Beaumont M (1993) Attenuation of colitis in the cotton-top tamarin by anti-α4 integrin monoclonal antibody. J Clin Invest 92:372–380

    Google Scholar 

  118. Pretolani M, Ruffie C, Lapa e Silva JR, Joseph D, Lobb RR, Vargaftig BB (1994) Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways. J Exp Med 180:795–805

    Google Scholar 

  119. Rabb HA, Olivenstein R, Issekutz TB, Renzi PM, Martin JG (1994) The role of the leukocyte adhesion molecules VLA-4, LFA-1, and Mac-1 in allergic airway responses in the rat. Am.J.Respir.Crit.Care Med. 149:1186–1191

    Google Scholar 

  120. Abraham WM, Sielczak MW, Ahmed A, Cortes A, Lauredo IT, Kim J, Pepinsky B, Benjamin CD, Leone DR, Lobb RR, Weller PF (1994) α4 Integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. J Clin Invest 93:776–787

    Google Scholar 

  121. Nakajima H, Sano H, Nishimura T, Yoshida S, Iwamoto I (1994) Role of vascular cell adhesion molecule 1/very late antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue. J Exp Med 179:1145–1154

    Google Scholar 

  122. Taichman DB, Cybulsky MI, Djaffar I, Longenecker BM, Teixido J, Rice GE, Aruffo A, Bevilacqua MP (1991) Tumor cell surface α4β1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. Cell Regul 2:347–355

    Google Scholar 

  123. Rice EG, Bevilacqua MP (1989) An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246:1303–1306

    Google Scholar 

  124. Qian F, Vaux D, Weissman IL (1994) Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell 77:335–347

    Google Scholar 

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  1. Institute for Medical Microbiology and Hygiene, Technical University, Trogerstrasse 4a, D-81675, Munich, Germany

    G. Kilger & B. Holzmann

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  1. G. Kilger
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  2. B. Holzmann
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Kilger, G., Holzmann, B. Molecular analysis of the physiological and pathophysiological role of α4-integrins. J Mol Med 73, 347–354 (1995). https://doi.org/10.1007/BF00192886

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  • DOI: https://doi.org/10.1007/BF00192886

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