A small molecule α4β1 antagonist prevents development of murine lyme arthritis without affecting protective immunity

Journal of Immunology

Volumn 175, Issue 7, 2005, Pages 4724-4734

  Gläsner, Joachim ^a   Blum, Horst ^b   Wehner, Volkmar ^b   Stilz, Hans Ulrich ^b   Humphries, Jonathan D ^c   Curley, G Paul ^c   Mould, A Paul ^c   Humphries, Martin J ^c   Hallmann, Rupert ^d   Röllinghoff, Martin ^a   Gessner, André ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b SANOFI AVENTIS DEUTSCHLAND GMBH   (Germany)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d LUND UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOOXYGENASE 2; FIBRONECTIN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2A; INTERLEUKIN 1; INTERLEUKIN 16; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; MESSENGER RNA; PRODRUG; RECEPTOR BLOCKING AGENT; S 16197; S 16204; S 18407; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VERY LATE ACTIVATION ANTIGEN 4;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANKLE; ANTIBACTERIAL ACTIVITY; ARTICLE; BORRELIA BURGDORFERI; CELL ADHESION; CELL MIGRATION; CONTROLLED STUDY; DRUG POTENCY; ENDOTHELIUM CELL; FEMALE; FLOW CYTOMETRY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IN VITRO STUDY; INFLAMMATION; INNATE IMMUNITY; LYME DISEASE; MOUSE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPIROCHETE; TH1 CELL;

EID: 25444508682     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.175.7.4724     Document Type: Article

References (89)

1. Sigal, L. H. 1997. Lyme disease: a review of aspects of its immunology and immunopathogenesis. Annu. Rev. Immunol. 15: 63-92.
2. Akin, E., J. Aversa, and A. C. Steere. 2001. Expression of adhesion molecules in synovia of patients with treatment-resistant lyme arthritis. Infect. Immun. 69: 1774-1780.
3. Barthold, S. W., D. H. Persing, A. L. Armstrong, and R. A. Peeples. 1991. Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Am. J. Pathol. 139: 263-273.
4. Muller, W. A. 2002. Leukocyte-endothelial cell interactions in the inflammatory response. Lab. Invest. 82: 521-533.
5. Ulbrich, H., E. E. Eriksson, and L. Lindbom. 2003. Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease. Trends Pharmacol. Sci. 24: 640-647.
6. Schenkel, A. R., Z. Mamdouh, and W. A. Muller. 2004. Locomotion of monocytes on endothelium is a critical step during extravasation. Nat. Immunol. 5: 393-400.
7. Schaible, U. E., D. Vestweber, E. G. Butcher, T. Stehle, and M. M. Simon. 1994. Expression of endothelial cell adhesion molecules in joints and heart during Borrelia burgdorferi infection of mice. Cell Adhes. Commun. 2: 465-479.
8. Seiler, K. P., Y. Ma, J. H. Weis, P. S. Frenette, R. O. Hynes, D. D. Wagner, and J. J. Weis. 1998. E and P selectins are not required for resistance to severe mutine lyme arthritis. Infect. Immun. 66: 4557-4559.
9. Boggemeyer, E., T. Stehle, U. E. Schaible, M. Hahne, D. Vestweber, and M. M. Simon. 1994. Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro. Cell Adhes. Commun. 2: 145-157.
10. Ebnet, K., K. D. Brown, U. K. Siebenlist, M. M. Simon, and S. Shaw. 1997. Borrelia burgdorferi activates nuclear factor-κB and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts. J. Immunol. 158: 3285-3292.
11. Sellati, T. J., M. J. Burns, M. A. Ficazzola, and M. B. Furie. 1995. Borrelia burgdorferi upregulates expression of adhesion molecules on endothelial cells and promotes transendothelial migration of neutrophils in vitro. Infect. Immun. 63: 4439-4447.
12. Sellati, T. J., L. D. Abrescia, J. D. Radolf, and M. B. Furie. 1996. Outer surface lipoproteins of Borrelia burgdorferi activate vascular endothelium in vitro. Infect. Immun. 64: 3180-3187.
13. Wooten, R. M., V. R. Modur, T. M. McIntyre, and J. J. Weis. 1996. Borrelia burgdorferi outer membrane protein A induces nuclear translocation of nuclear factor-κB and inflammatory activation in human endothelial cells. J. Immunol. 157: 4584-4590.
14. Burns, M. J., and M. B. Furie. 1998. Borrelia burgdorferi and interleukin-1 promote the transendothelial migration of monocytes in vitro by different mechanisms. Infect. Immun. 66: 4875-4883.
15. Hemler, M. E. 1990. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu. Rev. Immunol. 8: 365-400.
16. 4 integrins in vivo. J. Clin. Invest. 94: 1722-1728.
17. 1 integrins that mediate adhesion to extracellular matrix proteins. J. Immunol. 154: 6058-6064.
18. Bochner, B. S., S. A. Sterbinsky, M. Briskin, S. S. Saini, and D. W. MacGlashan, Jr. 1996. Counter-receptors on human basophils for endothelial cell adhesion molecules. J. Immunol. 157: 844-850.
19. + NK cells regulates their interaction with endothelial cells. Eur. J. Immunol. 34: 1333-1341.
20. 4-integrin: an alternative pathway for neutrophil recruitment? Immunol. Today 20: 545-550.
21. 4 integrin in the inflammatory response of neutrophils. J. Exp. Med. 194: 219-226.
22. 4 integrin and VCAM-1 in CD18-independent neutrophil migration across mouse cardiac endothelium. Circ. Res. 90: 562-569.
23. Tasaka, S., S. E. Richer, J. P. Mizgerd, and C. M. Doerschuk. 2002. Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice. Am. J. Respir. Crit. Care Med. 166: 53-60.
24. 4-integrin: a newly identified pathway of neutrophil recruitment in critically ill septic patients. Nat. Med. 7: 465-470.
25. Shimaoka, M., J. Takagi, and T. A. Springer. 2002. Conformational regulation of integrin structure and function. Annu. Rev. Biophys. Biomol. Struct. 31: 485-516.
26. Elices, M. J., L. Osborn, Y. Takada, C. Crouse, S. Luhowskyj, M. E. Hemler, and R. R. Lobb. 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.
27. Wayner, E. A., A. Garcia-Pardo, M. J. Humphries, J. A. McDonald, and W. G. Carter. 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.
28. 1 integrin. J. Cell Sci. 111: 1165-1174.
29. v-family integrins through novel integrin-binding mechanisms. Blood 98: 458-466.
30. 1. J. Exp. Med. 182: 345-355.
31. Isobe, T., T. Hisaoka, A. Shimizu, M. Okuno, S. Aimoto, Y. Takada, Y. Saito, and J. Takagi. 1997. Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. J. Biol. Chem. 272: 8447-8453.
32. 1: facilitation by JAM3. J. Biol. Chem. 277: 27589-27592.
33. Masumoto, A., and M. E. Hemler. 1993. Multiple activation states of VLA-4: mechanistic differences between adhesion to CS1/fibronectin and to vascular cell adhesion molecule-1. J. Biol. Chem. 268: 228-234.
34. Yang, G. X., and W. K. Hagmann. 2003. VLA-4 antagonists: potent inhibitors of lymphocyte migration. Med. Res. Rev. 23: 369-392.
35. 1 integrin. Nature 356: 63-66.
36. 4 subunit inhibit the murine contact hypersensitivity response. Eur. J. Immunol. 23: 682-688.
37. 4 integrin monoclonal antibody. J. Clin. Invest. 92: 372-380.
38. 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. J. Clin. Invest. 93: 776-787.
39. Seiffge, D. 1996. Protective effects of monoclonal antibody to VLA-4 on leukocyte adhesion and course of disease in adjuvant arthritis in rats. J. Rheumatol. 23: 2086-2091.
40. Miller, D. H., O. A. Khan, W. A. Sheremata, L. D. Blumhardt, G. P. Rice, M. A. Libonati, A. J. Willmer-Hulme, C. M. Dalton, K. A. Miszkiel, and P. W. O'Connor. 2003. A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl J. Med. 348: 15-23.
41. Ghosh, S., E. Goldin, F. H. Gordon, H. A. Malchow, J. Rask-Madsen, P. Rutgeerts, P. Vyhnalek, Z. Zadorova, T. Palmer, and S. Donoghue. 2003. Natalizumab for active Crohn's disease. N. Engl J. Med. 348: 24-32.
42. Lin, K. C., and A. C. Castro. 1998. Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents. Curr. Opin. Chem. Biol. 2: 453-457.
43. 1 antagonists. J. Pharmacol. Exp. Ther. 301: 747-752.
44. Koo, G. C., K. Shah, G. J. Ding, J. Xiao, R. Wnek, G. Doherty, X. C. Tong, R. B. Pepinsky, K. C. Lin, W. K. Hagmann, et al. 2003. A small molecule very late antigen-4 antagonist can inhibit ovalbumin-induced lung inflammation. Am. J. Respir. Crit. Care Med. 167: 1400-1409.
45. Theien, B. E., C. L. Vanderlugt, C. Nickerson-Nutter, M. Cornebise, D. M. Scott, S. J. Perper, E. T. Whalley, and S. D. Miller. 2003. Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE. Blood 102: 4464-4471.
46. Cannella, B., S. Gaupp, R. G. Tilton, and C. S. Raine. 2003. Differential efficacy of a synthetic antagonist of VLA-4 during the course of chronic relapsing experimental autoimmune encephalomyelitis. J. Neurosci. Res. 71: 407-416.
47. Williams, R. L., W. Risau, H. G. Zerwes, H. Drexler, A. Aguzzi, and E. F. Wagner. 1989. Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment. Cell 57: 1053-1063.
48. Montesano, R., M. S. Pepper, U. Mohle-Steinlein, W. Risau, E. F. Wagner, and L. Orci. 1990. Increased proteolytic activity is responsible for the aberrant morphogenetic behavior of endothelial cells expressing the middle T oncogene. Cell 62: 435-445.
49. Sundstrom, C., and K. Nilsson. 1976. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int. J. Cancer 17: 565-577.
50. Terhorst, C., P. Parham, D. L. Mann, and J. L. Strominger. 1976. Structure of HLA antigens: amino-acid and carbohydrate compositions and NH2-terminal sequences of four antigen preparations. Proc. Natl. Acad. Sci. USA 73: 910-914.
51. 2 integrins can generate different ligand binding states. Eur. J. Immunol. 25: 637-643.
52. Minowada, J., T. Onuma, and G. E. Moore. 1972. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J. Natl. Cancer Inst. 49: 891-895.
53. Rasheed, S., W. A. Nelson-Rees, E. M. Toth, P. Arnstein, and M. B. Gardner. 1974. Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer 33: 1027-1033.
54. Humphries, M. J. 2001. Cell adhesion assays. Mol. Biotechnol 18: 57-61.
55. Pollack, R. J., S. R. Telford, 3rd, and A. Spielman. 1993. Standardization of medium for culturing Lyme disease spirochetes. J. Clin. Microbiol. 31: 1251-1255.
56. Miller, L. C., E. A. Lynch, S. Isa, J. W. Logan, C. A. Dinarello, and A. C. Steere. 1993. Balance of synovial fluid IL-1β and IL-1 receptor antagonist and recovery from Lyme arthritis. Lancet 341: 146-148.
57. Beck, G., J. L. Benach, and G. S. Habicht. 1989. Isolation of interleukin 1 from joint fluids of patients with Lyme disease. J. Rheumatol. 16: 800-806.
58. Yang, L., Y. Ma, R. Schoenfeld, M. Griffiths, E. Eichwald, B. Araneo, and J. J. Weis. 1992. Evidence for B-lymphocyte mitogen activity in Borrelia burgdorferi-infected mice. Infect. Immun. 60: 3033-3041.
59. Anguita, J., S. Samanta, S. K. Ananthanarayanan, B. Revilla, G. P. Geba, S. W. Barthold, and E. Fikrig. 2002. Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. FEMS Immunol. Med. Microbiol. 34: 187-191.
60. Pahl, A., U. Kuhlbrandt, K. Brune, M. Rollinghoff, and A. Gessner. 1999. Quantitative detection of Borrelia burgdorferi by real-time PCR. J. Clin. Microbiol. 37: 1958-1963.
61. Montgomery, R. R. 2002. Now they eat them, now they don't: phagocytes and Borrelia burgdorferi in Lyme disease. Microbiol. Today 30: 165-166.
62. Keane-Myers, A., and S. P. Nickell. 1995. Role of IL-4 and IFN-γ in modulation of immunity to Borrelia burgdorferi in mice. J. Immunol. 155: 2020-2028.
63. Matyniak, J. E., and S. L. Reiner. 1995. T helper phenotype and genetic susceptibility in experimental Lyme disease. J. Exp. Med. 181: 1251-1254.
64. Liu, N., R. R. Montgomery, S. W. Barthold, and L. K. Bockenstedt. 2004. Myeloid differentiation antigen 88 deficiency impairs pathogen clearance but does not alter inflammation in Borrelia burgdorferi-infecied mice. Infect. Immun. 72: 3195-3203.
65. Brown, C. R., and S. L. Reiner. 1999. Experimental lyme arthritis in the absence of interleukin-4 or γ interferon. Infect. Immun. 67: 3329-3333.
66. Stetson, D. B., M. Mohrs, R. L. Reinhardt, J. L. Baron, Z. E. Wang, L. Gapin, M. Kronenberg, and R. M. Locksley. 2003. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J. Exp. Med. 198: 1069-1076.
67. Brown, C. R., V. A. Blaho, and C. M. Loiacono. 2003. Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2. J. Immunol. 171: 893-901.
68. Issekutz, T. B., M. Miyasaka, and A. C. Issekutz. 1996. Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation. J. Exp. Med. 183: 2175-2184.
69. 2) integrins modulate neutrophil caspase activation and survival following TNF-α or endotoxin induced transendothelial migration. Immunol. Cell Biol. 82: 435-446.
70. Tilley, J. W. 2002. VLA-4 antagonists. Expert Opinion on Therapeutic Patents 12: 991-1008.
71. 1-mediated melanoma cell adhesion and migration on vascular cell adhesion molecule-1 (VCAM-1) and the alternatively spliced IIICS region of fibronectin. J. Biol. Chem. 269: 27224-27230.
72. 1 integrin activation. J. Cell. Physiol. 175: 193-202.
73. Kettritz, R., M. Choi, S. Rolle, M. Wellner, and F. C. Luft. 2004. Integrins and cytokines activate nuclear transcription factor-κB in human neutrophils. J. Biol. Chem. 279: 2657-2665.
74. Jakus, Z., G. Berton, E. Ligeti, C. A. Lowell, and A. Mocsai. 2004. Responses of neutrophils to anti-integrin antibodies depends on costimulation through low affinity FcγRs: full activation requires both integrin and nonintegrin signals. J. Immunol. 173: 2068-2077.
75. 2+, exocytosis of azurophilic granules, quantitative up-regulation of CD18, shedding of L-selectin, and actin polymerization. J. Leukocyte Biol. 56: 625-635.
76. Morimoto, C., S. Iwata, and K. Tachibana. 1998. VLA-4-mediated signaling. Curr. Top. Microbiol. Immunol. 231: 1-22.
77. Autenrieth, I. B., V. Kempf, T. Sprinz, S. Preger, and A. Schnell. 1996. Defense mechanisms in Peyer's patches and mesenteric lymph nodes against Yersinia enterocolitica involve integrins and cytokines. Infect. Immun. 64: 1357-1368.
78. 4 integrin. J. Immunol. 151: 4790-4802.
79. 7 integrins selectively inhibits intestinal mast cell hyperplasia and worm expulsion in response to Nippostrongylus brasiliensis infection. Eur. J. Immunol. 31: 860-868.
80. Khan, S. B., A. R. Allen, G. Bhangal, J. Smith, R. R. Lobb, H. T. Cook, and C. D. Pusey. 2003. Blocking VLA-4 prevents progression of experimental crescentic glomerulonephritis. Nephron Exp. Nephrol. 95: e100-e110.
81. Butcher, E. C., M. Williams, K. Youngman, L. Rott, and M. Briskin. 1999. Lymphocyte trafficking and regional immunity. Adv. Immunol. 72: 209-253.
82. Kunkel, E. J., and E. C. Butcher. 2003. Plasma-cell homing. Nat. Rev. Immunol. 3: 822-829.
83. Autenrieth, I. B., U. Vogel, S. Preger, B. Heymer, and J. Heesemann. 1993. Experimental Yersinia enterocolitica infection in euthymic and T-cell-deficient athymic nude C57BL/6 mice: comparison of time course, histomorphology, and immune response. Infect. Immun. 61: 2585-2595.
84. - T-helper cells that are generated in the intestine. Immunology 66: 588-594.
85. Schaible, U. E., R. Wallich, M. D. Kramer, G. Nerz, T. Stehle, C. Museteanu, and M. M. Simon. 1994. Protection against Borrelia burgdorferi infection in SCID mice is conferred by presensitized spleen cells and partially by B but not T cells alone. Int. Immunol. 6: 671-681.
86. Fikrig, E., S. W. Barthold, F. S. Kantor, and R. A. Flavell. 1990. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science 250: 553-556.
87. Barthold, S. W., S. Feng, L. K. Bockenstedt, E. Fikrig, and K. Feen. 1997. Protective and arthritis-resolving activity in sera of mice infected with Borrelia burgdorferi. Clin. Infect. Dis. 1(Suppl. 25): S9-S17.
88. Sato, T., K. Tachibana, Y. Nojima, N. D'Avirro, and C. Morimoto. 1995. Role of the VLA-4 molecule in T cell costimulation: identification of the tyrosine phosphorylation pattern induced by the ligation of VLA-4. J. Immunol. 155: 2938-2947.
89. 1 (CD49d/CD29) integrin costimulation of human T cells enhances transcription factor and cytokine induction in the absence of altered sensitivity to anti-CD3 stimulation. J. Immunol. 157: 1965-1972.