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Adhesion Molecules in Inflammatory Diseases

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Abstract

Cell adhesion molecules (CAM) have a key role in the inflammatory response. Selectins, integrins and immunoglobulin (Ig) gene superfamily adhesion receptors mediate the different steps of the migration of leucocytes from the bloodstream towards inflammatory foci. The activation of endothelial cells (EC) upregulates the expression of several CAM and triggers the interaction of these cells with leucocytes. Selectins are involved in the initial interactions (tethering/rolling) of leucocytes with activated endothelium, whereas integrins and Ig superfamily CAM mediate the firm adhesion of these cells and their subsequent extravasation. During rolling, leucocytes are activated through the intracellular signals generated by CAM and chemokine receptors. Blockade of the function or expression of CAM has emerged as a new therapeutic target in inflammatory diseases. Different drugs are able to interfere with cell adhesion phenomena. In addition, new antiadhesion therapeutic approaches (blocking monoclonal antibodies, soluble receptors, synthetic peptides, peptidomimetics, etc.) are currently in development.

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References

  1. Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425–34

    Article  PubMed  CAS  Google Scholar 

  2. Frenette PS, Wagner DD. Adhesion molecules —part I. N Engl J Med 1996; 334: 1526–9

    Article  PubMed  CAS  Google Scholar 

  3. Frenette PS, Wagner DD. Adhesion molecules —part II: blood vessels and blood cells. N Engl J Med 1996; 335: 43–5

    Article  PubMed  CAS  Google Scholar 

  4. Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994; 84: 2068–101

    PubMed  CAS  Google Scholar 

  5. Kansas GS. Selectins and their ligands: current concepts and controversies. Blood 1996; 88: 3259–3287

    PubMed  CAS  Google Scholar 

  6. Rosen SD, Bertozzi CR. The selectins and their ligands. Curr Opin Cell Biol 1994; 6: 663–73

    Article  PubMed  CAS  Google Scholar 

  7. SteegmaierM, Levinovitz A, Isenmman S, et al. The E-selectinligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature 1995; 373: 615–20

    Article  Google Scholar 

  8. Brenner G, Gulbins E, Schlottman K, et al. L-selectin activates the Ras pathway via the tyrosine kinase p561ck. Proc Natl Acad Sci U S A 1996; 93: 15376–81

    Article  PubMed  CAS  Google Scholar 

  9. Lo SK, Golenbock DT, Sass PM, et al. Engagement of the Lewis X antigen (CD15) results in monocyte activation. Blood 1997; 89: 307–14

    PubMed  CAS  Google Scholar 

  10. Corbl AL. Leukocyte integrins, structure, expression and function. Heidelberg: Springer Verlag, 1996

    Google Scholar 

  11. Postigo AA, Teixidó J, Sánchez-Madrid F. The α4βl/VCAM-1 adhesion pathway in physiology and disease. Res Immunol 1993; 144: 723–35

    Article  PubMed  CAS  Google Scholar 

  12. Altevogt P, Hubbe M, Ruppert M, et al. The α4 integrin chain is a ligand for α4β7 and α4β1. J Exp Med 1995; 182: 345–55

    Article  PubMed  CAS  Google Scholar 

  13. Phillips DR, Charo FI, Parise L, et al. The platelet membrane glycoprotein lib-Ilia complex. Blood 1988; 71: 831–43

    PubMed  CAS  Google Scholar 

  14. Gawaz M, Neumann FJ, Dickfeld T, et al. Vitronectin receptor (alpha(v)beta3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction. Circulation 1997; 96: 1809–18

    Article  PubMed  CAS  Google Scholar 

  15. Sánchez-Mateos P, Cabañas C, Sánchez-Madrid F. Regulation of integrin function. Semin Cancer Biol 1996; 7: 99–109

    Article  PubMed  Google Scholar 

  16. Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995; 268: 233–8

    Article  PubMed  CAS  Google Scholar 

  17. Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol 1993; 120: 577–85

    Article  PubMed  CAS  Google Scholar 

  18. Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development 1988; 102: 639–55

    PubMed  CAS  Google Scholar 

  19. Bianchi E, Bender JR, Biasi F, et al. Through and beyond the wall: late steps in leukocyte transendothelial migration. Immunol Today 1997; 18: 586–91

    Article  PubMed  CAS  Google Scholar 

  20. Imai T, Hieshima K, Haskell C, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997; 91: 521–30

    Article  PubMed  CAS  Google Scholar 

  21. Rollins BJ. Chemokines. Blood 1997; 90: 909–28

    PubMed  CAS  Google Scholar 

  22. Bach FH, Hancock WW, Ferran C. Protective genes expressed in endothelial cells: a regulatory response to injury. Immunol Today 1997; 18: 483–6

    Article  PubMed  CAS  Google Scholar 

  23. Vassalli P. The pathophysiology of tumor necrosis factor. Annu Rev Immunol 1992; 10: 411–43

    Article  PubMed  CAS  Google Scholar 

  24. Heller RA, Krönke M. Tumor necrosis factor receptor mediated signaling pathways. J Cell Biol 1994; 126: 5–9

    Article  PubMed  CAS  Google Scholar 

  25. Baggiolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol 1997; 15: 675–705

    Article  PubMed  CAS  Google Scholar 

  26. Luster AD. Chemokines: chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436–45

    Article  PubMed  CAS  Google Scholar 

  27. Nieto M, Frade JMR, Sancho D, et al. Polarization of chemokine receptors to the leading edge during lymphocyte chemotaxis. J Exp Med 1997; 18: 153–8

    Article  Google Scholar 

  28. Ernofsson M, Siegbahn A. Platelet-derived growth factor-BB, and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor. Thromb Res 1996; 83: 307–20

    Article  PubMed  CAS  Google Scholar 

  29. Schecter AD, Rollins BJ, Zhang YJ, et al. Tissue factor is induced by monocyte chemotactic protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997: 272: 28568–73

    Article  PubMed  CAS  Google Scholar 

  30. Berlin C, Bargatze RF, Campbell JJ, et al. α4 Integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 1995; 80: 413–22

    Article  PubMed  CAS  Google Scholar 

  31. Johnston B, Issekutz TB, Kubes P. The alpha 4-integrin supports leukocyte rolling and adhesion in chronically inflamed postcapillary venules in vivo. J Exp Med 1996; 183: 1995–2006

    Article  PubMed  CAS  Google Scholar 

  32. Feng D, Nagy JA, Pyne K, et al. Neutrophils emigrate from venules by a transendothelial cell pathway in response to fMLP. J Exp Med 1998; 187: 903–15

    Article  PubMed  CAS  Google Scholar 

  33. Piali L, Hammel P, Uherek C, et al. CD31/PECAM-1 is a ligand for αvβ3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 1995; 130: 451–560

    Article  PubMed  CAS  Google Scholar 

  34. Dustin ML, Springer TA. Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Annu Rev Immunol 1991; 9: 27–66

    Article  PubMed  CAS  Google Scholar 

  35. Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 289–97

    Article  PubMed  CAS  Google Scholar 

  36. Henn V, Slupsky JR, Grafe M, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591–4

    Article  PubMed  CAS  Google Scholar 

  37. Diasio RB, Lo Buglio AR Immunomodulators: immunosup-pressive agents and immunostimulants. In: Hardman JG, Limbird LE, editors. Goodman & Gilman: the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 1291–308

    Google Scholar 

  38. Cronstein BN, Eberle MA, Gruber HE, et al. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci USA 1991; 18: 2441–52

    Article  Google Scholar 

  39. Cronstein BN, Nalme D, Ostud E, et al. The antiinflammatory mechanism of methotrexate; increased adenosine release at inflamed sites disminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92: 2675–89

    Article  PubMed  CAS  Google Scholar 

  40. Servitje O, Bordas X, Seron D, et al. Changes in T-cell pheno-type and adhesion molecules expression in psoriatic lesions after low-dose cyclosporin therapy. J Cutan Pathol 1996; 23: 431–6

    Article  PubMed  CAS  Google Scholar 

  41. Wheller SK, Perretti M. Dexamethasone inhibits cytokine-induced intercellular adhesion molecule-1 up-regulation on endothelial cell lines. Eur J Pharmacol 1997; 331: 65–71

    Article  PubMed  CAS  Google Scholar 

  42. Farsky SP, Sannomiya P, Garcia-Leme J. Secreted glucorticoids regulate leukocyte-endothelial interactions in inflammation: a direct vital microscopic study. J Leukoc Biol 1995; 57: 379–86

    PubMed  CAS  Google Scholar 

  43. Dimitrijevic M, Bartlett RR. Leflunomide, a novel immuno-modulating drug, inhibits homotypic adhesion of peripheral blood and synovial fluid mononuclear cells in rheumatoid arthritis. Inflamm Res 1996; 45: 550–5

    Article  PubMed  CAS  Google Scholar 

  44. Sekido N, Mukaida N, Harada A, et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 1993; 365: 654–57

    Article  PubMed  CAS  Google Scholar 

  45. Eigler A, Sinha B, Hartmann G, et al. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 1997; 18: 487–91

    Article  PubMed  CAS  Google Scholar 

  46. Osborn L, Vassallo C, Browning BG, et al. Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1). J Cell Biol 1994; 124: 601–8

    Article  PubMed  CAS  Google Scholar 

  47. Lee JO, Rieu P, Arnaout MA, et al. Crystal structure of the A domain from the alpha subunit of integrin CR3(CDllb/CD18). Cell 1995; 80: 631–8

    Article  PubMed  CAS  Google Scholar 

  48. Gahmberg CG, Tolvanen M, Nortamo P, et al. The intercellular adhesion molecules (ICAMs). In: Horton MA, editor. Adhesion receptors as therapeutic targets. Boca Raton: CRC Press, 1996: 37–58

    Google Scholar 

  49. Buckley CD, Simmons DL. Cell adhesion: a new target for theraphy. Mol Med Today 1997; 3: 449–56

    Article  PubMed  CAS  Google Scholar 

  50. Archelos JJ, Hartung HP. The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and therapeutic implications. Mol Med Today 1997; 3: 310–21

    Article  PubMed  CAS  Google Scholar 

  51. Cornejo CJ, Winn RK, Harlan JM. Anti-adhesion therapy. Adv Pharmacol 1997; 39: 99–142

    Article  PubMed  CAS  Google Scholar 

  52. Liao F, Ali J, Greene T, et al. Soluble domain 1 of platelet-endothelial cell adhesion molecule (PECAM) is sufficient to block transendothelial migration in vitro and in vivo. J Exp Med 1997; 185: 1349–57

    Article  PubMed  CAS  Google Scholar 

  53. Verstraete M, Zoldhelyi P. Novel antithrombotic drugs in development. Drugs 1995; 49: 856–84

    Article  PubMed  CAS  Google Scholar 

  54. Alig L, Edenhofer A, Hadvary P, et al. Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 1992; 35: 4393–407

    Article  PubMed  CAS  Google Scholar 

  55. Bernabei A, Gikakis N, Kowalska MA, et al. Iloprost and echistatin protect platelets during simulated extracorporeal circulation. Ann Thorac Surg 1995; 59: 149–53

    Article  PubMed  CAS  Google Scholar 

  56. Mausa SA, Bozarth JM, Forsythe MS, et al. Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist. Circulation 1994; 89: 3–12

    Article  Google Scholar 

  57. Higashi H, Suzuki Y, Mukaida N, et al. Intervention in endotoxin shock by sulfatide (I3SO3-GalCer) with a concomitant reduction in tumor necrosis factor alpha production. Infect Immun 1997; 65: 1223–7

    PubMed  CAS  Google Scholar 

  58. Shjmaoka M, Ikeda M, Iida T, et al. Fucoidin, a potent inhibitor of leukocyte rolling, prevents neutrophil influx into phorbolester-induced inflammatory sites in rabbit lungs. Am J Resp Crit Care Med 1996; 153; 307–11

    Google Scholar 

  59. Dlaz-González F, González-Alvaro I, Campanero MR, et al. Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs. J Clin Invest 1995; 95: 1756–65

    Article  Google Scholar 

  60. González-Alvaro I, Carmona L, Díaz-González F, et al. Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils. J Rheumatol 1996; 23: 723–9

    PubMed  Google Scholar 

  61. García-Vicuña R, Diaz-González F, González-Alvaro I, et al. Prevention of cytokine-induced changes in leukocyte adhesion receptors by nonsteroidal antiinflammatory drugs from oxicam family. Arthritis Rheum 1997; 40: 143–53

    Article  PubMed  Google Scholar 

  62. Dlaz-González F, Sánchez-Madrid F. Inhibition of leukocyte adhesion: an alternative mechanism of action for antiinflammatory drugs. Immunol Today 1998; 19: 169–72

    Article  Google Scholar 

  63. Koike R, Miki I, Otoshi M, et al. Gold sodium thiomalate down-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on vascular endothelial cells. Mol Pharmacol 1994; 46: 599–604

    PubMed  CAS  Google Scholar 

  64. Gadangi P, Longaker M, Naime D, et al. The antiinflammatory mechanisms of sulfasalazine is related to adenosine release at inflamed sites. J Immunol 1996; 156: 1937–41

    PubMed  CAS  Google Scholar 

  65. Cronstein BN, Molad Y, Reibman J, et al. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest 1995; 96: 994–1002

    Article  PubMed  CAS  Google Scholar 

  66. Zhou L, Pope BL, Chourmouzis E, et al. Tepoxalin blocks neutrophil migration into cutaneous inflammatory sites by inhibiting Mac-1 and E-selectin expression. Eur J Immunol 1996; 26: 120–9

    Article  PubMed  CAS  Google Scholar 

  67. Panes J, Russell JM, Wolf RE, et al. Effects of tenidap on leukocyte-endothelial cell adhesion in mesenteric venules. J Rheumatol 1995; 22: 444–9

    PubMed  CAS  Google Scholar 

  68. Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994; 265: 956–9

    Article  PubMed  CAS  Google Scholar 

  69. Khachigian LM, Collins T, Fries JW. N-acetyl cysteine blocks mesangial VCAM-1 and NF-kappa B expression in. vivo. Am J Pathol 1997; 151: 1225–9

    PubMed  CAS  Google Scholar 

  70. Read MA, Neish AS, Luscinskas FW, et al. The proteasome pathway is required for cytokine-induced endothelial-leukocyte adhesion molecule expression. Immunity 1995; 2: 493–506

    Article  PubMed  CAS  Google Scholar 

  71. Mazzone A, Mazzucchelli I, Fossati G, et al. Iloprost effects on phagocytes in patients suffering from ischaemic diseases: in vivo evidence for down-regulation of alpha M beta 2 integrin. Eur J Clin Invest 1996; 26: 860–6

    Article  PubMed  CAS  Google Scholar 

  72. Weber C, Erl W, Weber KS, et al. HMG-CoA reductase inhibitors decrease CDllb expression and CDllb-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hyper-cholesterolemia. J Am Coll Cardiol 1997; 30: 1212–7

    Article  PubMed  CAS  Google Scholar 

  73. Cominacini L, Garbin U, Pasini AF, et al. Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells. Free Radic Biol Med 1997; 22: 117–27

    Article  PubMed  CAS  Google Scholar 

  74. Torphy TJ, Barnette MS, Hay DW, et al. Phosphodiesterase IV inhibitors as therapy for eosinophil-induced lung injury in asthma. Environ Health Perspect 1994; 102 Suppl.: 79–84

    PubMed  Google Scholar 

  75. Ciprandi G, Buscaglia S, Pesce G, et al. Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early-and late-phase reactions after allergen-specific challenge. J Allergy Clin Immunol 1995; 95: 612–21

    Article  PubMed  CAS  Google Scholar 

  76. Hamilton GS, Mewshaw RE, Bryant CM, et al. Fluorenyalkanoic and benzoic acids as novel inhibitors of cell adhesion processes in leukocytes. J Med Chem 1995; 38: 1650–6

    Article  PubMed  CAS  Google Scholar 

  77. Endemann G, Feng Y, Bryant CM, et al. Novel anti-inflammatory compounds prevent CD11b/CD18, alpha M beta 2 (Mac-1)-dependent neutrophil adhesion without blocking activation-induced changes in Mac-1. J Pharmacol Exp Ther 1996; 276: 5–12

    PubMed  CAS  Google Scholar 

  78. González-Amaro R, Portales-Pérez D, Baranda L, et al. Pentoxifylline inhibits adhesion and activation of human T lymphocytes. J Immunol 1998 1 Jul; 161: 65–72

    PubMed  Google Scholar 

  79. Kovach NL, Lindgren CG, Fefer A, et al. Pentoxifylline inhibits integrin-mediated adherence of interleukin-2-activated human peripheral blood lymphocytes to human umbilical vein endothelial cells, matrix components, and cultured tumor cells. Blood 1994; 84: 2234–42

    PubMed  CAS  Google Scholar 

  80. Agrawal S. Antisense oligonucleotides: towards clinical trials. Trends Biotechnol 1996; 14: 376–87

    Article  PubMed  CAS  Google Scholar 

  81. Bennett CF, Kornbrust D, Henry S, et al. An ICAM-1 antisense oligonucleotide prevents and reverses dextran sulfate sodium-induced colitis in mice. J Pharmacol Exp Ther 1997; 280: 988–1000

    PubMed  CAS  Google Scholar 

  82. Stepkowski SM, Tu Y, Condon TP, et al. Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense aligonucleotides alone or in combination with other immunosuppressive modalities. J Immunol 1994; 153: 5336–46

    PubMed  CAS  Google Scholar 

  83. Glover JM, Leeds JM, Mant TG, et al. Phase I safety and pharmacokinetics profile of an intercellular adhesion molecule-1 antisense oligonucleotide (ISIS 2302). J Pharmacol Exp Ther 1997; 282: 1173–80

    PubMed  CAS  Google Scholar 

  84. Agrawal S, Iyer RP. Perspectives in antisense therapeutics. Pharmacol Ther 1997; 76: 151–60

    Article  PubMed  CAS  Google Scholar 

  85. Morishita R, Sugimoto T, Aoki M, et al. In. vivo transfection of cis element ‘decoy’ against nuclear factor-kappaB binding site prevents myocardial infarction. Nat Med 1997; 3: 894–9

    Article  PubMed  CAS  Google Scholar 

  86. Claude H. The anti-gene strategy: control of gene expression by triplex-forming oligonucleotides. Anticancer Drug Des 1991; 6: 569–84

    Google Scholar 

  87. Suitters AJ, Foulkes R, Opal SM, et al. Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock. J Exp Med 1994; 179: 849–56

    Article  PubMed  CAS  Google Scholar 

  88. Abraham E, Wunderink R, Silverman H, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor α in patients with sepsis syndrome: a randomized, controlled, double-blind, multicenter clinical trial. JAMA 1995; 273: 934–41

    Article  PubMed  CAS  Google Scholar 

  89. Fisher Jr CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. N Engl J Med 1996; 334: 1697–702

    Article  PubMed  CAS  Google Scholar 

  90. Fisher Jr CJ, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: results from a randomized, double-blind, placebo-controlled trial. JAMA 1994; 271: 1836–43

    Article  PubMed  Google Scholar 

  91. Ikeda N, Mukaida N, Kaneko S, et al. Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin β2 with concomitant reduction of cytokine production. Infect Immun 1995; 63: 4812–7

    PubMed  CAS  Google Scholar 

  92. Watanabe S, Mukaida N, Ikeda N, et al. Prevention of endotoxin shock by an antibody against leukocyte integrin beta 2 through inhibiting production and action of TNF. Int Immunol 1995; 7: 1037–46

    Article  PubMed  CAS  Google Scholar 

  93. Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease: Crohn’s disease study group. N Engl J Med 1997; 337: 1029–35

    Article  PubMed  CAS  Google Scholar 

  94. Stack WA, Mann SD, Roy AJ, et al. Randomised controlled trial of CDP571 antibody to tumor necrosis factor-alpha in Crohn’s disease. Lancet 1997; 349: 521–4

    Article  PubMed  CAS  Google Scholar 

  95. Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337: 141–7

    Article  PubMed  CAS  Google Scholar 

  96. Elliot MJ, Maini RN, Feldmann M, et al. Repeated therapy with monoclonal antibody to tumour necrosis factor a (cA2) in patients with rheumatoid arthritis. Lancet 1994; 344: 1125–7

    Article  Google Scholar 

  97. Tak PP, Taylor PC, Breedveld FC, et al. Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum 1996; 39: 1077–81

    Article  PubMed  CAS  Google Scholar 

  98. Paleolog EM, Hunt M, Elliot MJ, et al. Deactivation of vascular endothelium bymonoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis. Arthritis Rheum 1996; 39: 1082–91

    Article  PubMed  CAS  Google Scholar 

  99. Kavanaugh AF, Schulze-Koops H, Davis LS, et al. Repeat treatment of rheumatoid arthritis patients with a murine anti-intercellular adhesion molecule 1 monoclonal antibody. Arthritis Rheum 1997; 40: 849–53

    Article  PubMed  CAS  Google Scholar 

  100. Davis LS, Kavanaugh AF, Nichols LA, et al. Induction of persistent T cell hyporesponsiveness in. vivo by monoclonal antibody to ICAM-1 in patients with rheumatoid arthritis. J Immunol 1995; 154: 3525–37

    PubMed  CAS  Google Scholar 

  101. Jasin HE, Lightfoot E, Davis LS, et al. Amelioration of antigen-induced arthritis in rabbits treated with monoclonal antibodies to leukocyte adhesion molecules. Arthritis Rheum 1992; 35: 541–49

    Article  PubMed  CAS  Google Scholar 

  102. Barbadillo C, G-Arroyo A, Salas C, et al. Anti-integrin immuno-therapy in rheumatoid arthritis: protective effect of anti-alpha 4 antibody in adjuvant arthritis. Springer Semin Immunopathol 1995; 16: 427–36

    Article  PubMed  CAS  Google Scholar 

  103. Issekutz AC, Ayer L, Miyasaka M, et al. Treatment of stablished adjuvant arthritis in rats with monoclonal antibody to CD18 and very late activation antigen-4 integrins suppresses neutro-phil and T-lymphocyte migration to the joints and improves clinical disease. Immunology 1996; 88: 569–76

    Article  PubMed  CAS  Google Scholar 

  104. McFadden Jr ER, Gilbert IA. Asthma. N Engl J Med 1992; 327: 1928–37

    Article  PubMed  Google Scholar 

  105. Wardlaw AJ, Walsh GM, Symon FA. Adhesion interactions involved in eosinophil migration through vascular endothelium. Ann N Y Acad Sci 1996; 796: 124–37

    Article  PubMed  CAS  Google Scholar 

  106. Takafuji S, Ohtoshi T, Takizawa H, et al. Eosinophil degranulation in the presence of epithelial cells. Effect of cytokines and role of adhesion. J Immunol 1996; 156: 3980–5

    CAS  Google Scholar 

  107. Wegner CD, Gundel RH, Reoly P, et al. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science 1990; 247: 456–9

    Article  PubMed  CAS  Google Scholar 

  108. Gundel RH, Wegner CD, Torcellini CA, et al. Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys. J Clin Invest 1991; 88: 1407–11

    Article  PubMed  CAS  Google Scholar 

  109. Abraham WM, Sielczak MW, Ahmed A, et al. Alpha-4 integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. J Clin Invest 1994; 93: 776–87

    Article  PubMed  CAS  Google Scholar 

  110. Pretolani M, Ruffe C, Lapa-e-Silva JR, et al. Antibody to very late activation antigen-4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in guinea pig airways. J Exp Med 1994; 180: 795–805

    Article  PubMed  CAS  Google Scholar 

  111. Featherstone C. Anti-integrin drugs developed to treat inflammation. Lancet 1996; 347: 1106

    Article  PubMed  CAS  Google Scholar 

  112. Herstenberg PE, Winsor-Hines D, Briskin MJ, et al. Rapid resolution of chronic colitis in the cotton-top tamarin with an antibody to a gut-homing integrin alpha 4 beta 7. Gastroenterology 1996; 111: 1373–80

    Article  Google Scholar 

  113. Picarella D, Hurlbut P, Rottman J, et al. Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MadCAM-1) reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells. J Immunol 1997; 158: 2099–106

    PubMed  CAS  Google Scholar 

  114. del Zoppo GJ, Wagner S, Tagaya M. Trends and future developments in the pharmacological treatment of acute ischemie stroke. Drugs 1997; 54: 9–38

    Article  PubMed  Google Scholar 

  115. Birnbaum Y, Patterson M, Kloner RA. The effect of CY1503, a sialyl Lewisx analog blocker of the selectin adhesion molecules, on infarct size and ’no-reflow’ in the rabbit model of acute myocardial infarction/reperfusion. J Mol Cell Cardiol 1997; 29: 2013–25

    Article  PubMed  CAS  Google Scholar 

  116. Buerke M, Weyrich AS, Zheng Z, et al. Sialyl Lewisx-containing oligosaccharide attenuates myocardial reperfusion injury in cats. J Clin Invest 1994; 93: 1140–8

    Article  PubMed  CAS  Google Scholar 

  117. Silver MJ, Sutton JM, Hook S, et al. Adjunctive selectin blockade succesfully reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model. Circulation 1995; 92: 492–9

    Article  PubMed  CAS  Google Scholar 

  118. Flynn DM, Buda AJ, Jeffords PR, et al. A sialyl Lewisx-containing carbohydrate reduces infarct size: role of selectins in myocardial reperfusion injury. Am J Physiol 1996; 271: H2086–96

    PubMed  CAS  Google Scholar 

  119. Weiser MR, Gibbs SA, Valeri CR, et al. Anti-selectin therapy modifies skeletal muscle ischemia and reperfusion injury. Shock 1996; 5: 402–7

    Article  PubMed  CAS  Google Scholar 

  120. Takada M, Nadeau KC, Shaw GD, et al. Prevention of late renal changes after initial ischemia/reperfusion injury by blocking early selectin binding. Transplantation 1997; 64: 1520–5

    Article  PubMed  CAS  Google Scholar 

  121. Simoons ML, Rutsch W, Vahanian A, et al. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997; 349: 1429–35

    Article  Google Scholar 

  122. Zhao ZQ, Lefer DJ, Sato H, et al. Monoclonal antibody to ICAM-1 preserves postischemic blood flow and reduces infarct size after ischemia/reperfusion in rabbit. J Leukoc Biol 1997; 62: 292–300

    PubMed  CAS  Google Scholar 

  123. Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1 and p150/95 glycoproteins. Annu Rev Med 1987; 38: 175–94

    Article  PubMed  CAS  Google Scholar 

  124. Etzioni A, Phillips LM, Paulson JC, et al. Leukocyte adhesion deficiency (LAD) II. Ciba Found Symp 1995; 189: 51–8

    PubMed  CAS  Google Scholar 

  125. Kuijpers TW, van Lier RAW, Hamann D, et al. Leukocyte adhesion deficiency type 1 (LAD-1)/variant. J Clin Invest 1997; 100: 1725–33

    Article  PubMed  CAS  Google Scholar 

  126. Sharar S, Sasaki SS, Flaherty LC, et al. P-selectin blockade does not impair leukocyte host defense against bacterial peritonitis and soft tissue infection in rabbits. J Immunol 1993; 151: 4982–8

    PubMed  CAS  Google Scholar 

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González-Amaro, R., Diaz-González, F. & Sánchez-Madrid, F. Adhesion Molecules in Inflammatory Diseases. Drugs 56, 977–988 (1998). https://doi.org/10.2165/00003495-199856060-00003

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