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Adhesion molecules as therapeutic targets

  • Mark R. Nicolls
  • Rasa Tamosiuniene
Part of the Progress in Inflammation Research book series (PIR)

Abstract

The immunoglobulin supergene family (IgSF) cell adhesion molecules (CAMs) are either homophilic or heterophilic proteins that bind either integrins or different IgSF CAMs. Proteins are classified into the IgSF if they possess a structural domain known as an Ig domain, which contain about 70–110 amino acids and are categorized into different types according to their size and function [1]. Members of this family with important adhesion function include CD2, CD48, the SIGLEC family (sialic acid binding Ig-like lectins such as CD22, CD83), intracellular adhesion molecules (ICAMs), vascular cell adhesion molecule (VCAM-1), platelet-endothelial cell adhesion molecule (PECAM-1), neural cell adhesion molecules (NCAMs), L1-CAM and CHL-1. NCAMs, L1-CAM and CHL-1 are important proteins for neurological cell adhesion. Members of the IgSF are ligands for the integrins, and so these can be considered together conceptually with this class of CAMs. IgSF members have not been as extensively targeted as have integrin proteins, and the broad utility of these agents are largely undetermined. A summary of selected pre-clinical studies and clinical trials is presented in Table 1. Anti-ICAM therapy has proven neutral or possibly deleterious in a stroke trial [2]. Anti-CD2 therapy has shown efficacy against graft vs. host disease [3], but this is likely due to lymphocyte and natural killer cell depletion rather than anti-adhesion effects.

Keywords

Progressive Multifocal Leukoencephalopathy Islet Allograft Immune Synapse Integrin Antagonist Natural Killer Cell Depletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Barclay A (2003) Membrane proteins with immunoglobulin-like domains — a master superfamily of interaction molecules. Semin Immunol 15: 215–223PubMedCrossRefGoogle Scholar
  2. 2.
    Enlimomab Acute Stroke Trial Investigators (2001) Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57: 1428–1434Google Scholar
  3. 3.
    Spitzer TR, McAfee SL, Dey BR, Colby C, Hope J, Grossberg H, Preffer F, Shaffer J, Alexander SI, Sachs DH et al (2003) Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies. Transplantation 75: 1748–1751PubMedCrossRefGoogle Scholar
  4. 4.
    Yonekawa K, Harlan JM (2005) Targeting leukocyte integrins in human diseases. J Leukoc Biol 77: 129–140PubMedCrossRefGoogle Scholar
  5. 5.
    Nicolls MR, Gill RG (2006) LFA-1 (CD11a) as a therapeutic target. Am J Transplant 6: 27–36PubMedCrossRefGoogle Scholar
  6. 6.
    Davignon D, Martz E, Reynolds T, Kurzinger K, Springer TA (1981) Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci USA 78: 4535–4539PubMedCrossRefGoogle Scholar
  7. 7.
    Sanchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci USA 79: 7489–7493PubMedCrossRefGoogle Scholar
  8. 8.
    Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C (2002) JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 3: 151–158PubMedCrossRefGoogle Scholar
  9. 9.
    Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 76: 301–314PubMedCrossRefGoogle Scholar
  10. 10.
    Bachmann MF, McKall-Faienza K, Schmits R, Bouchard D, Beach J, Speiser DE, Mak TW, Ohashi PS (1997) Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. Immunity 7: 549–557PubMedCrossRefGoogle Scholar
  11. 11.
    Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285: 221–227PubMedCrossRefGoogle Scholar
  12. 12.
    Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295: 1539–1542PubMedCrossRefGoogle Scholar
  13. 13.
    Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395: 82–86PubMedCrossRefGoogle Scholar
  14. 14.
    Qi SY, Groves JT, Chakraborty AK (2001) Synaptic pattern formation during cellular recognition. Proc Natl Acad Sci USA 98: 6548–6553PubMedCrossRefGoogle Scholar
  15. 15.
    Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller DM, Kupfer A (2002) Staging and resetting T cell activation in SMACs. Nat Immunol 3: 911–917PubMedCrossRefGoogle Scholar
  16. 16.
    Huang J, Lo PF, Zal T, Gascoigne NR, Smith BA, Levin SD, Grey HM (2002) CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse. Proc Natl Acad Sci USA 99: 9369–9373PubMedCrossRefGoogle Scholar
  17. 17.
    Pribila JT, Quale AC, Mueller KL, Shimizu Y (2004) Integrins and T cell-mediated immunity. Annu Rev Immunol 22: 157–180PubMedCrossRefGoogle Scholar
  18. 18.
    Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA, Shaw S (1988) Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol 140: 1401–1407PubMedGoogle Scholar
  19. 19.
    Lee WT, Vitetta ES (1991) The differential expression of homing and adhesion molecules on virgin and memory T cells in the mouse. Cell Immunol 132: 215–222PubMedCrossRefGoogle Scholar
  20. 20.
    Okumura M, Fujii Y, Takeuchi Y, Inada K, Nakahara K, Matsuda H (1993) Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population. Eur J Immunol 23: 1057–1063PubMedCrossRefGoogle Scholar
  21. 21.
    Moy VT, Brian AA (1992) Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells: enhanced antigen presentation after stimulation through LFA-1. J Exp Med 175: 1–7PubMedCrossRefGoogle Scholar
  22. 22.
    Howard DR, Eaves AC, Takei F (1986) Lymphocyte function-associated antigen (LFA-1) is involved in B cell activation. J Immunol 136: 4013–4018PubMedGoogle Scholar
  23. 23.
    Fischer A, Durandy A, Sterkers G, Griscelli C (1986) Role of the LFA-1 molecule in cellular interactions required for antibody production in humans. J Immunol 136: 3198–3203PubMedGoogle Scholar
  24. 24.
    Owens T (1991) A role for adhesion molecules in contact-dependent T help for B cells. Eur J Immunol 21: 979–983PubMedCrossRefGoogle Scholar
  25. 25.
    Metzler B, Gfeller P, Bigaud M, Li J, Wieczorek G, Heusser C, Lake P, Katopodis A (2004) Combinations of anti-LFA-1, everolimus, anti-CD40 ligand, and allogeneic bone marrow induce central transplantation tolerance through hemopoietic chimerism, including protection from chronic heart allograft rejection. J Immunol 173: 7025–7036PubMedGoogle Scholar
  26. 26.
    Yamagami S, Isobe M, Yamagami H, Hori J, Tsuru T (1997) Rejection mechanism and immunosuppression by FK 506 and anti-leukocyte function associated antigen-1 antibody in concordant corneal xenotransplantation. Transplant Proc 29: 943–944PubMedCrossRefGoogle Scholar
  27. 27.
    Rayat GR, Gill RG (2005) Indefinite survival of neonatal porcine islet xenografts by simultaneous targeting of LFA-1 and CD154 or CD45RB. Diabetes 54: 443–451PubMedCrossRefGoogle Scholar
  28. 28.
    Kavanaugh AF, Lightfoot E, Lipsky PE, Oppenheimer-Marks N (1991) Role of CD11/ CD18 in adhesion and transendothelial migration of T cells. Analysis utilizing CD18-deficient T cell clones. J Immunol 146: 4149–4156PubMedGoogle Scholar
  29. 29.
    Hamann A, Jablonski-Westrich D, Duijvestijn A, Butcher EC, Baisch H, Harder R, Thiele HG (1988) Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J Immunol 140: 693–699PubMedGoogle Scholar
  30. 30.
    Warnock RA, Askari S, Butcher EC, von Andrian UH (1998) Molecular mechanisms of lymphocyte homing to peripheral lymph nodes. J Exp Med 187: 205–216PubMedCrossRefGoogle Scholar
  31. 31.
    Constantin G, Majeed M, Giagulli C, Piccio L, Kim JY, Butcher EC, Laudanna C (2000) Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 13: 759–769PubMedCrossRefGoogle Scholar
  32. 32.
    Andrew DP, Spellberg JP, Takimoto H, Schmits R, Mak TW, Zukowski MM (1998) Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice. Eur J Immunol 28: 1959–1969PubMedCrossRefGoogle Scholar
  33. 33.
    Belperio JA, Keane MP, Burdick MD, Gomperts B, Xue YY, Hong K, Mestas J, Ardehali A, Mehrad B, Saggar R et al (2005) Role of CXCR2/CXCR2 ligands in vascular remodeling during bronchiolitis obliterans syndrome. J Clin Invest 115: 1150–1162PubMedCrossRefGoogle Scholar
  34. 34.
    Berlin PJ, Bacher JD, Sharrow SO, Gonzalez C, Gress RE (1992) Monoclonal antibodies against human T cell adhesion molecules — Modulation of immune function in nonhuman primates. Transplantation 53: 840–849PubMedCrossRefGoogle Scholar
  35. 35.
    Vugmeyster Y, Kikuchi T, Lowes MA, Chamian F, Kagen M, Gilleaudeau P, Lee E, Howell K, Bodary S, Dummer W et al (2004) Efalizumab (anti-CD11a)-induced increase in peripheral blood leukocytes in psoriasis patients is preferentially mediated by altered trafficking of memory CD8+ T cells into lesional skin. Clin Immunol 113: 38–46PubMedCrossRefGoogle Scholar
  36. 36.
    Van Seventer GA, Shimizu Y, Horgan KJ, Shaw S (1990) The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 144: 4579–4586PubMedGoogle Scholar
  37. 37.
    Zuckerman LA, Pullen L, Miller J (1998) Functional consequences of costimulation by ICAM-1 on IL-2 gene expression and T cell activation. J Immunol 160: 3259–3268PubMedGoogle Scholar
  38. 38.
    Cai Z, Brunmark A, Jackson MR, Loh D, Peterson PA, Sprent J (1996) Transfected Drosophilia cells as a probe for defining the minimal requirements for stimulating unprimed CD8+ T cells. Proc Natl Acad Sci USA 93: 14736–14741PubMedCrossRefGoogle Scholar
  39. 39.
    Abraham C, Griffith J, Miller J (1999) The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand. J Immunol 162: 4399–4405PubMedGoogle Scholar
  40. 40.
    Ragazzo JL, Ozaki ME, Karlsson L, Peterson PA, Webb SR (2001) Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells. Proc Natl Acad Sci USA 98: 241–246PubMedCrossRefGoogle Scholar
  41. 41.
    Bleijs DA, van Duijnhoven GC, van Vliet SJ, Thijssen JP, Figdor CG, van Kooyk Y (2001) A single amino acid in the cytoplasmic domain of the beta 2 integrin lymphocyte function-associated antigen-1 regulates avidity-dependent inside-out signaling. J Biol Chem 276: 10338–10346PubMedCrossRefGoogle Scholar
  42. 42.
    Chatila TA, Geha RS, Arnaout MA (1989) Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules. J Cell Biol 109: 3435–3444PubMedCrossRefGoogle Scholar
  43. 43.
    Rovere P, Inverardi L, Bender JR, Pardi R (1996) Feedback modulation of ligandengaged alpha L/beta 2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase. J Immunol 156: 2273–2279PubMedGoogle Scholar
  44. 44.
    Wulfing C, Sjaastad MD, Davis MM (1998) Visualizing the dynamics of T cell activation: intracellular adhesion molecule 1 migrates rapidly to the T cell/B cell interface and acts to sustain calcium levels. Proc Natl Acad Sci USA 95: 6302–6307PubMedCrossRefGoogle Scholar
  45. 45.
    Bianchi E, Denti S, Granata A, Bossi G, Geginat J, Villa A, Rogge L, Pardi R (2000) Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature 404: 617–621PubMedCrossRefGoogle Scholar
  46. 46.
    Perez OD, Mitchell D, Jager GC, South S, Murriel C, McBride J, Herzenberg LA, Kinoshita S, Nolan GP (2003) Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1. Nat Immunol 4: 1083–1092PubMedCrossRefGoogle Scholar
  47. 47.
    Nicolls MR, Coulombe M, Yang H, Bolwerk A, Gill RG (2000) Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. J Immunol 164: 3627–3634PubMedGoogle Scholar
  48. 48.
    Nicolls MR, Coulombe M, Beilke J, Gelhaus HC, Gill RG (2002) CD4-dependent generation of dominant transplantation tolerance induced by simultaneous perturbation of CD154 and LFA-1 pathways. J Immunol 169: 4831–4839PubMedGoogle Scholar
  49. 49.
    Salomon B, Bluestone JA (1998) LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. J Immunol 161: 5138–5142PubMedGoogle Scholar
  50. 50.
    Jenks SA, Eisfelder BJ, Miller J (2005) LFA-1 co-stimulation inhibits Th2 differentiation by down-modulating IL-4 responsiveness. Int Immunol 17: 315–323PubMedCrossRefGoogle Scholar
  51. 51.
    Luksch CR, Winqvist O, Ozaki ME, Karlsson L, Jackson MR, Peterson PA, Webb SR (1999) Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells. Proc Natl Acad Sci USA 96: 3023–3028PubMedCrossRefGoogle Scholar
  52. 52.
    Da Silva M, Petruzzo P, Virieux S, Tiollier J, Badet L, Martin X (2001) A primate model of renal ischemia-reperfusion injury for preclinical evaluation of the antileukocyte function associated antigen 1 monoclonal antibody odulimonab. J Urol 166: 1915–1919PubMedCrossRefGoogle Scholar
  53. 53.
    Cavazzana-Calvo M, Sarnacki S, Haddad E, De Coene C, Calise D, Yvon E, Cerf-Bensussan N, Fischer A (1995) Prevention of bone marrow and cardiac graft rejection in an H-2 haplotype disparate mouse combination by an anti-LFA-1 antibody. Transplantation 59: 1576–1582PubMedCrossRefGoogle Scholar
  54. 54.
    Bashuda H, Takazawa K, Tamatani T, Miyasaka M, Yagita H, Okumura K (1996) Induction of persistent allograft tolerance in the rat by combined treatment with antileukocyte function-associated antigen-1 and anti-intercellular adhesion molecule-1 monoclonal antibodies, donor-specific transfusion, and FK506. Transplantation 62: 117–122PubMedCrossRefGoogle Scholar
  55. 55.
    Miwa S, Isobe M, Suzuki J, Makuuchi M, Miyasaka M, Yamazaki S, Kawasaki S (1997) Effect of anti-intercellular adhesion molecule-1 and anti-leukocyte function associated antigen-1 monoclonal antibodies on rat-to-mouse cardiac xenograft rejection. Surgery 121: 681–689PubMedCrossRefGoogle Scholar
  56. 56.
    Isobe M, Yagita H, Okumura K, Ihara A (1992) Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 255: 1125–1127PubMedCrossRefGoogle Scholar
  57. 57.
    Horimoto H, Ito T, Hayashi T, Miyasaka M, Nozawa M (1998) Transplantation tolerance by a combined therapy with sulfatide, anti-LFA-1/ICAM-1 monoclonal antibodies and FK506 in rat cardiac transplantation. Transpl Int 11(Suppl 1): S310–312PubMedCrossRefGoogle Scholar
  58. 58.
    Harrison PC, Madwed JB (1999) Anti-LFA-1 alpha reduces the dose of cyclosporin A needed to produce immunosuppression in heterotopic cardiac transplanted rats. J Heart. Lung Transplant 18: 279–284PubMedCrossRefGoogle Scholar
  59. 59.
    Corbascio M, Mahanty H, Osterholm C, Qi Z, Pearson TC, Larsen CP, Freise CE, Ekberg H (2002) Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice. Transplantation 74: 35–41PubMedCrossRefGoogle Scholar
  60. 60.
    Poston RS, Robbins RC, Chan B, Simms P, Presta L, Jardieu P, Morris RE (2000) Effects of humanized monoclonal antibody to rhesus CD11a in rhesus monkey cardiac allograft recipients. Transplantation 69: 2005–2013PubMedCrossRefGoogle Scholar
  61. 61.
    Corbascio M, Ekstrand H, Osterholm C, Qi Z, Simanaitis M, Larsen CP, Pearson TC, Riesbeck K, Ekberg H (2002) CTLA4Ig combined with anti-LFA-1 prolongs cardiac allograft survival indefinitely. Transpl Immunol 10: 55–61PubMedCrossRefGoogle Scholar
  62. 62.
    Morikawa M, Brazelton TR, Berry GJ, Morris RE (2001) Prolonged inhibition of obliterative airway disease in murine tracheal allografts by brief treatment with anti-leukocyte function-associated antigen-1 (CD11a) monoclonal antibody. Transplantation 71:1616–1621PubMedCrossRefGoogle Scholar
  63. 63.
    Murakawa T, Kerklo MM, Zamora MR, Wei Y, Gill RG, Henson PM, Grover FL, Nicolls MR (2005) Simultaneous LFA-1 and CD40 ligand antagonism prevents airway remodeling in orthotopic airway transplantation: implications for the role of respiratory epithelium as a modulator of fibrosis. J Immunol 174: 3869–3879PubMedGoogle Scholar
  64. 64.
    Nakao Y, Mackinnon SE, Strasberg SR, Hertl MC, Isobe M, Susskind BM, Mohanakumar T, Hunter DA (1995) Immunosuppressive effect of monoclonal antibodies to ICAM-1 and LFA-1 on peripheral nerve allograft in mice. Microsurgery 16: 612–620PubMedCrossRefGoogle Scholar
  65. 65.
    Genden EM, Mackinnon SE, Yu S, Flye MW (1998) Induction of donor-specific tolerance to rat nerve allografts with portal venous donor alloantigen and anti-ICAM-1/LFA-1 monoclonal antibodies. Surgery 124: 448–456PubMedGoogle Scholar
  66. 66.
    Larsson LC, Corbascio M, Widner H, Pearson TC, Larsen CP, Ekberg H (2002) Simultaneous inhibition of B7 and LFA-1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L. Xenotransplantation 9: 68–76PubMedCrossRefGoogle Scholar
  67. 67.
    Isobe M, Suzuki J, Yamazaki S, Sekiguchi M (1996) Acceptance of primary skin graft after treatment with anti-intercellular adhesion molecule-1 and anti-leukocyte function-associated antigen-1 monoclonal antibodies in mice. Transplantation 62: 411–413PubMedCrossRefGoogle Scholar
  68. 68.
    He Y, Mellon J, Apte R, Niederkorn JY (1994) Effect of LFA-1 and ICAM-1 antibody treatment on murine corneal allograft survival. Invest Ophthalmol Vis Sci 35: 3218–3225PubMedGoogle Scholar
  69. 69.
    Hori J, Isobe M, Yamagami S, Mizuochi T, Tsuru T (1997) Specific immunosuppression of corneal allograft rejection by combination of anti-VLA-4 and anti-LFA-1 monoclonal antibodies in mice. Exp Eye Res 65: 89–98PubMedCrossRefGoogle Scholar
  70. 70.
    Kato Y, Yamataka A, Yagita H, Bashuda H, Okumura K, Miyano T (1995) Prevention of fetal bowel allograft rejection by combined treatment with anti-ICAM-1 and anti-LFA-1 antibodies. J Pediatr Surg 30: 1093–1097PubMedCrossRefGoogle Scholar
  71. 71.
    Bowles MJ, Pockley AG, Wood RF (2000) Effect of anti-LFA-1 monoclonal antibody on rat small bowel allograft survival and circulating leukocyte populations. Transpl. Immunol 8: 75–80PubMedCrossRefGoogle Scholar
  72. 72.
    Gotoh M, Fukuzaki T, Monden M, Dono K, Kanai T, Yagita H, Okumura K, Mori T (1994) A potential immunosuppressive effect of anti-lymphocyte function-associated antigen-1 monoclonal antibody on islet transplantation. Transplantation 57: 123–126PubMedGoogle Scholar
  73. 73.
    Nishihara M, Gotoh M, Ohzato H, Ohta Y, Luo Z, Dono K, Umeshita K, Sakon M, Monden M, Yagita H et al (1997) Awareness of donor alloantigens in antiadhesion therapy induces antigen-specific unresponsiveness to islet allografts. Transplantation 64:965–970PubMedCrossRefGoogle Scholar
  74. 74.
    Arai K, Sunamura M, Wada Y, Takahashi M, Kobari M, Kato K, Yagita H, Okumura K, Matsuno S (1999) Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection. Int J Pancreatol 26: 23–31PubMedGoogle Scholar
  75. 75.
    Nicolls MR, Coulombe M, Diamond AS, Beilke J, Gill RG (2002) Interferon-gamma is not a universal requirement for islet allograft survival. Transplantation 74: 472–477PubMedCrossRefGoogle Scholar
  76. 76.
    Grochowiecki T, Gotoh M, Dono K, Takeda Y, Sakon M, Yagita H, Okumura K, Miyasaka M, Monden M (2000) Induction of unresponsiveness to islet xenograft by MMC treatment of graft and blockage of LFA-1/ICAM-1 pathway. Transplantation 69:1567–1571PubMedCrossRefGoogle Scholar
  77. 77.
    Berney T, Pileggi A, Molano RD, Poggioli R, Zahr E, Ricordi C, Inverardi L (2003) The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic islet grafts in nonobese diabetic mice. Transplantation 76: 1669–1674PubMedCrossRefGoogle Scholar
  78. 78.
    Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Gray GS, Vallera DA (1995) Coblockade of the LFA1:ICAM and CD28/CTLA4:B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts. Blood 85: 2607–2618PubMedGoogle Scholar
  79. 79.
    Wang Y, Gao D, Lunsford KE, Frankel WL, Bumgardner GL (2003) Targeting LFA-1 synergizes with CD40/CD40L blockade for suppression of both CD4-dependent and CD8-dependent rejection. Am J Transplant 3: 1251–1258PubMedCrossRefGoogle Scholar
  80. 80.
    Guerette B, Skuk D, Celestin F, Huard C, Tardif F, Asselin I, Roy B, Goulet M, Roy R, Entman M et al (1997) Prevention by anti-LFA-1 of acute myoblast death following transplantation. J Immunol 159: 2522–2531PubMedGoogle Scholar
  81. 81.
    Hasegawa Y, Yokono K, Taki T, Amano K, Tominaga Y, Yoneda R, Yagi N, Maeda S, Yagita H, Okumura K et al (1994) Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb. Int Immunol 6:831–838PubMedCrossRefGoogle Scholar
  82. 82.
    Chowdhury SA, Nagata M, Yamada K, Nakayama M, Chakrabarty S, Jin Z, Kotani R, Yokono K (2002) Tolerance mechanisms in murine autoimmune diabetes induced by anti-ICAM-1/LFA-1 mAb and anti-CD8 mAb. Kobe J Med Sci 48: 167–175PubMedGoogle Scholar
  83. 83.
    Cavazzana-Calvo M, Bordigoni P, Michel G, Esperou H, Souillet G, Leblanc T, Stephan JL, Vannier JP, Mechinaud F, Reiffers J et al (1996) A phase II trial of partially incompatible bone marrow transplantation for high-risk acute lymphoblastic leukaemia in children: prevention of graft rejection with anti-LFA-1 and anti-CD2 antibodies. Societe Francaise de Greffe de Moelle Osseuse. Br J Haematol 93: 131–138PubMedCrossRefGoogle Scholar
  84. 84.
    Maraninchi D, Mawas C, Stoppa AM, Gaspard MH, Marit G, Van Ekthoven A, Reiffers J, Olive D, Hirn M, Delaage M et al (1989) Anti LFA1 monoclonal antibody for the prevention of graft rejection after T cell-depleted HLA-matched bone marrow transplantation for leukemia in adults. Bone Marrow Transplant 4: 147–150PubMedGoogle Scholar
  85. 85.
    Le Mauff B, Hourmant M, Rougier JP, Hirn M, Dantal J, Baatard R, Cantarovich D, Jacques Y, Soulillou JP (1991) Effect of anti-LFA1 (CD11a) monoclonal antibodies in acute rejection in human kidney transplantation. Transplantation 52: 291–296PubMedCrossRefGoogle Scholar
  86. 86.
    Hourmant M, Bedrossian J, Durand D, Lebranchu Y, Renoult E, Caudrelier P, Buffet R, Soulillou JP (1996) A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations. Transplantation 62: 1565–1570PubMedCrossRefGoogle Scholar
  87. 87.
    Benfield MR, Tejani A, Harmon WE, McDonald R, Stablein DM, McIntosh M, Rose S (2005) A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation. Pediatr Transplant 9: 282–292PubMedCrossRefGoogle Scholar
  88. 88.
    Werther WA, Gonzalez TN, O’Connor SJ, McCabe S, Chan B, Hotaling T, Champe M, Fox JA, Jardieu PM, Berman PW et al (1996) Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1. J Immunol 157: 4986–4995PubMedGoogle Scholar
  89. 89.
    Vincenti F, Mendez R, Pescovitz M, Rajagopalan PR, Wilkinson AH, Butt K, Laskow D, Slakey DP, Lorber MI, Garg JP et al (2007) A Phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant 7: 1770–1777PubMedCrossRefGoogle Scholar
  90. 90.
    Gabrijelcic J, Acuna A, Profita M, Paterno A, Chung KF, Vignola AM, Rodriguez-Roisin R (2003) Neutrophil airway influx by platelet-activating factor in asthma: role of adhesion molecules and LTB4 expression. Eur Respir J 22: 290–297PubMedCrossRefGoogle Scholar
  91. 91.
    Xu B, Wagner N, Pham LN, Magno V, Shan Z, Butcher EC, Michie SA (2003) Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways. J Exp Med 197:1255–1267PubMedCrossRefGoogle Scholar
  92. 92.
    Gauvreau GM, Becker AB, Boulet LP, Chakir J, Fick RB, Greene WL, Killian KJ, O’Byrne P M, Reid JK, Cockcroft DW (2003) The effects of an anti-CD11a mAb, efaligracazumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma. J Allergy Clin Immunol 112: 331–338PubMedCrossRefGoogle Scholar
  93. 93.
    Chou YK, Edwards DM, Weinberg AD, Vandenbark AA, Kotzin BL, Fontenot AP, Burrows GG (2005) Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis. J Immunol 174: 4316–4324PubMedGoogle Scholar
  94. 94.
    Leonardi CL (2003) Efalizumab: an overview. J Am Acad Dermatol 49: S98–104PubMedCrossRefGoogle Scholar
  95. 95.
    Stern RS (2003) A promising step forward in psoriasis therapy. JAMA 290: 3133–3135PubMedCrossRefGoogle Scholar
  96. 96.
    Mittelbrunn M, Molina A, Escribese MM, Yanez-Mo M, Escudero E, Ursa A, Tejedor R, Mampaso F, Sanchez-Madrid F (2004) VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. Proc Natl Acad Sci USA 101: 11058–11063PubMedCrossRefGoogle Scholar
  97. 97.
    von Andrian UH, Engelhardt B (2003) Alpha4 integrins as therapeutic targets in autoimmune disease. N Engl J Med 348: 68–72CrossRefGoogle Scholar
  98. 98.
    Engelhardt B, Ransohoff RM (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 26: 485–495PubMedCrossRefGoogle Scholar
  99. 99.
    Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354: 899–910PubMedCrossRefGoogle Scholar
  100. 100.
    Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354: 911–923PubMedCrossRefGoogle Scholar
  101. 101.
    Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, Verbeeck J, Geboes K, Robberecht W, Rutgeerts P (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353: 362–368PubMedCrossRefGoogle Scholar
  102. 102.
    Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E et al (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354: 924–933PubMedCrossRefGoogle Scholar
  103. 103.
    Ley K (2001) Functions of selectins. Results Probl Cell Differ 33: 177–200PubMedGoogle Scholar
  104. 104.
    Foxall C, Watson SR, Dowbenko D, Fennie C, Lasky LA, Kiso M, Hasegawa A, Asa D, Brandley BK (1992) The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide. J Cell Biol 117: 895–902PubMedCrossRefGoogle Scholar
  105. 105.
    Slee DH, Romano SJ, Yu J, Nguyen TN, John JK, Raheja NK, Axe FU, Jones TK, Ripka WC (2001) Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinflammatory activity. J Med Chem 44: 2094–2107PubMedCrossRefGoogle Scholar
  106. 106.
    Ulbrich H, Eriksson EE, Lindbom L (2003) Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease. Trends Pharmacol Sci 24: 640–647PubMedCrossRefGoogle Scholar
  107. 107.
    Wienrich BG, Krahn T, Schon M, Rodriguez ML, Kramer B, Busemann M, Boehncke WH, Schon MP (2006) Structure-function relation of efomycines, a family of small-molecule inhibitors of selectin functions. J Invest Dermatol 126: 882–889PubMedCrossRefGoogle Scholar
  108. 108.
    Zhu GD, Arendsen DL, Gunawardana IW, Boyd SA, Stewart AO, Fry DG, Cool BL, Kifle L, Schaefer V, Meuth J et al (2001) Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)thieno[2, 3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 44: 3469–3487PubMedCrossRefGoogle Scholar
  109. 109.
    Salmela K, Wramner L, Ekberg H, Hauser I, Bentdal O, Lins LE, Isoniemi H, Backman L, Persson N, Neumayer HH et al (1999) A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group. Transplantation 67: 729–736PubMedCrossRefGoogle Scholar
  110. 110.
    Justicia C, Martin A, Rojas S, Gironella M, Cervera A, Panes J, Chamorro A, Planas AM (2006) Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice. J Cereb Blood Flow Metab 26: 421–432PubMedCrossRefGoogle Scholar
  111. 111.
    Gumina RJ, el Schultz J, Yao Z, Kenny D, Warltier DC, Newman PJ, Gross GJ (1996) Antibody to platelet/endothelial cell adhesion molecule-1 reduces myocardial infarct size in a rat model of ischemia-reperfusion injury. Circulation 94: 3327–3333PubMedGoogle Scholar
  112. 112.
    Murohara T, Delyani JA, Albelda SM, Lefer AM (1996) Blockade of platelet endothelial cell adhesion molecule-1 protects against myocardial ischemia and reperfusion injury in cats. J Immunol 156: 3550–3557PubMedGoogle Scholar
  113. 113.
    Isobe M, Suzuki J, Yamazaki S, Yazaki Y, Horie S, Okubo Y, Maemura K, Yazaki Y, Sekiguchi M (1997) Regulation by differential development of Th1 and Th2 cells in peripheral tolerance to cardiac allograft induced by blocking ICAM-1/LFA-1 adhesion. Circulation 96: 2247–2253PubMedGoogle Scholar
  114. 114.
    Bloemen PG, Buckley TL, van den Tweel MC, Henricks PA, Redegeld FA, Koster AS, Nijkamp FP (1996) LFA-1, and not Mac-1, is crucial for the development of hyperreactivity in a murine model of nonallergic asthma. Am J Respir Crit Care Med 153: 521–529PubMedGoogle Scholar
  115. 115.
    Theien BE, Vanderlugt CL, Eagar TN, Nickerson-Nutter C, Nazareno R, Kuchroo VK, Miller SD (2001) Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. J Clin Invest 107: 995–1006PubMedCrossRefGoogle Scholar
  116. 116.
    Theien BE, Vanderlugt CL, Nickerson-Nutter C, Cornebise M, Scott DM, Perper SJ, Whalley ET, Miller SD (2003) Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE. Blood 102: 4464–4471PubMedCrossRefGoogle Scholar
  117. 117.
    Dubree NJ, Artis DR, Castanedo G, Marsters J, Sutherlin D, Caris L, Clark K, Keating SM, Beresini MH, Chiu H et al (2002) Selective alpha4beta7 integrin antagonists and their potential as antiinflammatory agents. J Med Chem 45: 3451–3457PubMedCrossRefGoogle Scholar
  118. 118.
    Faxon DP, Gibbons RJ, Chronos NA, Gurbel PA, Sheehan F (2002) The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study. J Am Coll Cardiol 40: 1199–1204PubMedCrossRefGoogle Scholar
  119. 119.
    Targan SR, Feagan BG, Fedorak RN, Lashner BA, Panaccione R, Present DH, Spehlmann ME, Rutgeerts PJ, Tulassay Z, Volfova M et al (2007) Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE Trial. Gastroenterology 132: 1672–1683PubMedCrossRefGoogle Scholar
  120. 120.
    Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, Vyhnalek P, Zadorova Z, Palmer T, Donoghue S (2003) Natalizumab for active Crohn’s disease. N Engl J Med 348: 24–32PubMedCrossRefGoogle Scholar
  121. 121.
    Gordon FH, Lai CW, Hamilton MI, Allison MC, Srivastava ED, Fouweather MG, Donoghue S, Greenlees C, Subhani J, Amlot PL et al (2001) A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn’s disease. Gastroenterology 121: 268–274PubMedCrossRefGoogle Scholar
  122. 122.
    Ravensberg AJ, Luijk B, Westers P, Hiemstra PS, Sterk PJ, Lammers JW, Rabe KF (2006) The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma. Allergy 61: 1097–1103PubMedCrossRefGoogle Scholar
  123. 123.
    Beeh KM, Beier J, Meyer M, Buhl R, Zahlten R, Wolff G (2006) Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial. Pulm Pharmacol Ther 19: 233–241PubMedCrossRefGoogle Scholar
  124. 124.
    Langer R, Wang M, Stepkowski SM, Hancock WW, Han R, Li P, Feng L, Kirken RA, Berens KL, Dupre B et al (2004) Selectin inhibitor bimosiamose prolongs survival of kidney allografts by reduction in intragraft production of cytokines and chemokines. J Am Soc Nephrol 15: 2893–2901PubMedCrossRefGoogle Scholar
  125. 125.
    Oostingh GJ, Ludwig RJ, Enders S, Gruner S, Harms G, Boehncke WH, Nieswandt B, Tauber R, Schon MP (2007) Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule-or antibody-mediated inhibition of L-selectin functions. J Invest Dermatol 127: 90–97PubMedCrossRefGoogle Scholar
  126. 126.
    Oostingh GJ, Pozgajova M, Ludwig RJ, Krahn T, Boehncke WH, Nieswandt B, Schon MP (2007) Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody-or small-molecule-mediated inhibition of selectin-dependent platelet functions. Haematologica 92: 502–512PubMedCrossRefGoogle Scholar
  127. 127.
    Schermerhorn ML, Tofukuji M, Khoury PR, Phillips L, Hickey PR, Sellke FW, Mayer JE Jr, Nelson DP (2000) Sialyl lewis oligosaccharide preserves cardiopulmonary and endothelial function after hypothermic circulatory arrest in lambs. J Thorac Cardiovasc Surg 120: 230–237PubMedCrossRefGoogle Scholar
  128. 128.
    Kerr KM, Auger WR, Marsh JJ, Comito RM, Fedullo RL, Smits GJ, Kapelanski DP, Fedullo PF, Channick RN, Jamieson SW et al (2000) The use of cylexin (CY-1503) in prevention of reperfusion lung injury in patients undergoing pulmonary thromboendarterectomy. Am J Respir Crit Care Med 162: 14–20PubMedGoogle Scholar
  129. 129.
    Mocco J, Choudhri T, Huang J, Harfeldt E, Efros L, Klingbeil C, Vexler V, Hall W, Zhang Y, Mack W et al (2002) HuEP5C7 as a humanized monoclonal anti-E/P-selectin neurovascular protective strategy in a blinded placebo-controlled trial of nonhuman primate stroke. Circ Res 91: 907–914PubMedCrossRefGoogle Scholar
  130. 130.
    Bhushan M, Bleiker TO, Ballsdon AE, Allen MH, Sopwith M, Robinson MK, Clarke C, Weller RP, Graham-Brown RA, Keefe M et al (2002) Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial. Br J Dermatol 146: 824–831PubMedCrossRefGoogle Scholar
  131. 131.
    Lefer DJ (2000) Pharmacology of selectin inhibitors in ischemia/reperfusion states. Annu Rev Pharmacol Toxicol 40: 283–294PubMedCrossRefGoogle Scholar
  132. 132.
    Papayianni A, Serhan CN, Phillips ML, Rennke HG, Brady HR (1995) Transcellular biosynthesis of lipoxin A4 during adhesion of platelets and neutrophils in experimental immune complex glomerulonephritis. Kidney Int 47: 1295–1302PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Mark R. Nicolls
    • 1
  • Rasa Tamosiuniene
    • 1
  1. 1.Departments of Medicine and Division of Pulmonary and Critical Care MedicineVeterans Administration Palo Alto, Stanford UniversityPalo AltoUSA

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