An LFA-1 (αLβ2) small-molecule antagonist reduces inflammation and joint destruction in murine models of arthritis

Journal of Immunology

Volumn 184, Issue 7, 2010, Pages 3917-3926

  Suchard, Suzanne J ^a   Stetsko, Dawn K ^a   Davis, Patricia M ^a   Skala, Stacey ^a   Potin, Dominique ^b,c   Launay, Michele ^b   Dhar, T G Murali ^a   Barrish, Joel C ^a   Susulic, Vojkan ^a   Shuster, David J ^a   McIntyre, Kim W ^a   McKinnon, Murray ^a,d   Salter Cid, Luisa ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b CEREP   (France)

^c Laboratoires Fournier SA   (France)

^d CENTOCOR INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BMS 587101; CYTOKINE; IMMUNOMODULATING AGENT; INTERCELLULAR ADHESION MOLECULE 1; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; MESSENGER RNA; UNCLASSIFIED DRUG; 5 (9 (4 CYANOPHENYL) 3 (3,5 DICHLOROPHENYL) 1 METHYL 2,4 DIOXO 1,3,7 TRIAZASPIRO(4,4)NON 7 YLMETHYL) 3 THIOPHENECARBOXYLIC ACID; 5-(9-(4-CYANOPHENYL)-3-(3,5-DICHLOROPHENYL)-1-METHYL-2,4-DIOXO-1,3,7-TRIAZASPIRO(4,4)NON-7-YLMETHYL)-3-THIOPHENECARBOXYLIC ACID; ANTIINFLAMMATORY AGENT; SPIRO COMPOUND; THIOPHENE DERIVATIVE;

ADOLESCENT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN EXPRESSION; ARTHRITIS; ARTICLE; AUTOIMMUNE DISEASE; BONE DESTRUCTION; CELL ADHESION; CONTROLLED STUDY; CROSS REACTION; CYTOKINE PRODUCTION; DRUG BIOAVAILABILITY; DRUG POTENCY; ENDOTHELIUM CELL; FEMALE; GENE DELETION; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; JOINT DESTRUCTION; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RHEUMATOID ARTHRITIS; T LYMPHOCYTE; TH1 CELL; ANIMAL; BIOSYNTHESIS; CELL PROLIFERATION; DISEASE MODEL; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOLOGY; INFLAMMATION; METABOLISM; MIXED LYMPHOCYTE CULTURE; PATHOLOGY;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ARTHRITIS, EXPERIMENTAL; CELL ADHESION; CELL PROLIFERATION; CYTOKINES; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; INFLAMMATION; LYMPHOCYTE CULTURE TEST, MIXED; LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MICE; SPIRO COMPOUNDS; THIOPHENES;

EID: 77951624546     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901095     Document Type: Article

References (55)

1. Dubey, C., M. Croft, and S. L. Swain. 1995. Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response. J. Immunol. 155: 45-57.
2. Dustin, M. L., T. G. Bivona, and M. R. Philips. 2004. Membranes as messengers in T cell adhesion signaling. Nat. Immunol. 5: 363-372.
3. Sims, T. N., and M. L. Dustin. 2002. The immunological synapse: integrins take the stage. Immunol. Rev. 186: 100-117.
4. Wülfing, C., and M. M. Davis. 1998. A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science 282: 2266-2269. (Pubitemid 29004077)
5. Griffiths, E. K., C. Krawczyk, Y. Y. Kong, M. Raab, S. J. Hyduk, D. Bouchard, V. S. Chan, I. Kozieradzki, A. J. Oliveira-Dos-Santos, A. Wakeham, et al. 2001. Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science 293: 2260-2263.
6. Peterson, E. J., M. L. Woods, S. A. Dmowski, G. Derimanov, M. S. Jordan, J. N. Wu, P. S. Myung, Q. H. Liu, J. T. Pribila, B. D. Freedman, et al. 2001. Coupling of the TCR to integrin activation by Slap-130/Fyb. Science 293: 2263-2265.
7. Abraham, C., J. Griffith, and J. Miller. 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: 4399-4405. (Pubitemid 29314835)
8. Bianchi, E., S. Denti, A. Granata, G. Bossi, J. Geginat, A. Villa, L. Rogge, and R. Pardi. 2000. Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature 404: 617-621. (Pubitemid 30205061)
9. Perez, O. D., D. Mitchell, G. C. Jager, S. South, C. Murriel, J. McBride, L. A. Herzenberg, S. Kinoshita, and G. P. Nolan. 2003. Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1. Nat. Immunol. 4: 1083-1092.
10. 2+ levels. J. Immunol. 149: 3872-3880.
11. Berlin-Rufenach, C., F. Otto, M. Mathies, J. Westermann, M. J. Owen, A. Hamann, and N. Hogg. 1999. Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice. J. Exp. Med. 189: 1467-1478.
12. Shaw, S. K., S. Ma, M. B. Kim, R. M. Rao, C. U. Hartman, R. M. Froio, L. Yang, T. Jones, Y. Liu, A. Nusrat, et al. 2004. Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration. J. Exp. Med. 200: 1571-1580.
13. Sánchez-Martín, L., N. Sánchez-Sánchez, M. D. Gutiérrez-López, A. I. Rojo, M. Vicente-Manzanares, M. J. Pérez-Alvarez, P. Sánchez-Mateos, X. R. Bustelo, A. Cuadrado, F. Sánchez-Madrid, et al. 2004. Signaling through the leukocyte integrin LFA-1 in T cells induces a transient activation of Rac-1 that is regulated by Vav and PI3K/Akt-1. J. Biol. Chem. 279: 16194-16205.
14. Firestein, G. S. 2003. Evolving concepts of rheumatoid arthritis. Nature 423: 356-361.
15. Ding, Z. M., J. E. Babensee, S. I. Simon, H. Lu, J. L. Perrard, D. C. Bullard, X. Y. Dai, S. K. Bromley, M. L. Dustin, M. L. Entman, et al. 1999. Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J. Immunol. 163: 5029-5038.
16. Mine, S., T. Tabata, Y. Wada, T. Fujisaki, T. Iida, N. Noguchi, E. Niki, T. Kodama, and Y. Tanaka. 2002. Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and transendothelial migration of monocytes via the protein kinase C pathway. Atherosclerosis 160: 281-288.
17. Plescia, J., and D. C. Altieri. 1996. Activation of Mac-1 (CD11b/CD18)-bound factor X by released cathepsin G defines an alternative pathway of leucocyte initiation of coagulation. Biochem. J. 319: 873-879. (Pubitemid 26386203)
18. Kakimoto, K., T. Nakamura, K. Ishii, T. Takashi, H. Iigou, H. Yagita, K. Okumura, and K. Onoue. 1992. The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis. Cell. Immunol. 142: 326-337.
19. Kagari, T., H. Doi, and T. Shimozato. 2002. The importance of IL-1 β and TNFα, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritis. J. Immunol. 169: 1459-1466. (Pubitemid 34809191)
20. Kyburz, D., and M. Corr. 2003. The KRN mouse model of inflammatory arthritis. Springer Semin. Immunopathol. 25: 79-90.
21. Watts, G. M., F. J. Beurskens, I. Martin-Padura, C. M. Ballantyne, L. B. Klickstein, M. B. Brenner, and D. M. Lee. 2005. Manifestations of inflammatory arthritis are critically dependent on LFA-1. J. Immunol. 174: 3668-3675.
22. Potin, D., M. Launay, F. Monatlik, P. Malabre, M. Fabreguettes, A. Fouquet, M. Maillet, E. Nicolai, L. Dorgeret, F. Chevallier, et al. 2006. Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl) -1-methyl-2, 4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl]-3- thiophenecarboxylic acid (BMS-587101) - a small molecule antagonist of leukocyte function associated antigen-1. J. Med. Chem. 49: 6946-6949.
23. Malm, H., M. Corbascio, C. Osterholm, S. Cowan, C. P. Larsen, T. C. Pearson, and H. Ekberg. 2002. CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice. Transplantation 73: 293-297. (Pubitemid 34112856)
24. Edwards, C. P., M. Champe, T. Gonzalez, M. E. Wessinger, S. A. Spencer, L. G. Presta, P. W. Berman, and S. C. Bodary. 1995. Identification of amino acids in the CD11a I-domain important for binding of the leukocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule-1 (ICAM-1). J. Biol. Chem. 270: 12635-12640.
25. Winquist, R. J., S. Desai, S. Fogal, N. A. Haynes, G. H. Nabozny, P. L. Reilly, D. Souza, and M. Panzenbeck. 2001. The role of leukocyte function-associated antigen-1 in animal models of inflammation. Eur. J. Pharmacol. 429: 297-302.
26. Ogletree, M. L., D. N. Harris, W. A. Schumacher, M. L. Webb, and R. N. Misra. 1993. Pharmacological profile of BMS 180,291: a potent, long-acting, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist. J. Pharmacol. Exp. Ther. 264: 570-578.
27. Wang, X., R. T. Dorsam, A. Lauver, H. Wang, F. A. Barbera, S. Gibbs, D. Varon, N. Savion, S. M. Friedman, and G. Z. Feuerstein. 2002. Comparative analysis of various platelet glycoprotein IIb/IIIa antagonists on shear-induced platelet activation and adhesion. J. Pharmacol. Exp. Ther. 303: 1114-1120.
28. Månsson, B., D. Carey, M. Alini, M. Ionescu, L. C. Rosenberg, A. R. Poole, D. Heinegård, and T. Saxne. 1995. Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. J. Clin. Invest. 95: 1071-1077.
29. Yusuf-Makagiansar, H., M. E. Anderson, T. V. Yakovleva, J. S. Murray, and T. J. Siahaan. 2002. Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases. Med. Res. Rev. 22: 146-167.
30. Leuker, C. E., M. Labow, W. Müller, and N. Wagner. 2001. Neonatally induced inactivation of the vascular cell adhesion molecule 1 gene impairs B cell localization and T cell-dependent humoral immune response. J. Exp. Med. 193: 755-768.
31. Faveeuw, C., M. E. Di Mauro, A. A. Price, and A. Ager. 2000. Roles of alpha(4) integrins/VCAM-1 and LFA-1/ICAM-1 in the binding and transendothelial migration of T lymphocytes and T lymphoblasts across high endothelial venules. Int. Immunol. 12: 241-251.
32. Altieri, D. C., J. H. Morrissey, and T. S. Edgington. 1988. Adhesive receptor Mac-1 coordinates the activation of factor X on stimulated cells of monocytic and myeloid differentiation: an alternative initiation of the coagulation protease cascade. Proc. Natl. Acad. Sci. USA 85: 7462-7466.
33. Hynes, R. O. 1992. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69: 11-25.
34. Springer, T. A. 1995. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol. 57: 827-872.
35. Vetvicka, V., B. P. Thornton, and G. D. Ross. 1996. Soluble β-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J. Clin. Invest. 98: 50-61.
36. Herman, A., J. W. Kappler, P. Marrack, and A. M. Pullen. 1991. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu. Rev. Immunol. 9: 745-772.
37. Gartlehner, G., R. A. Hansen, B. L. Jonas, P. Thieda, and K. N. Lohr. 2006. The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J. Rheumatol. 33: 2398-2408. (Pubitemid 46067817)
38. 1 in models of hypersensitivity and arthritis. J. Clin. Invest. 105: 721-729.
39. Mankin, H. J., H. Dorfman, L. Lippiello, and A. Zarins. 1971. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J. Bone Joint Surg. Am. 53: 523-537.
40. 2 receptors in the pathogenesis of rheumatoid arthritis. J. Clin. Invest. 110: 651-658.
41. Vingsbo-Lundberg, C., T. Saxne, H. Olsson, and R. Holmdahl. 1998. Increased serum levels of cartilage oligomeric matrix protein in chronic erosive arthritis in rats. Arthritis Rheum. 41: 544-550. (Pubitemid 28128780)
42. Joosten, L. A., M. M. Helsen, T. Saxne, F. A. van De Loo, D. Heinegard, and W. B. van Den Berg. 1999. IL-1 α β blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-α blockade only ameliorates joint inflammation. J. Immunol. 163: 5049-5055.
43. Kelly, T. A., D. D. Jeanfavre, D. W. McNeil, J. R. Woska, Jr., P. L. Reilly, E. A. Mainolfi, K. M. Kishimoto, G. H. Nabozny, R. Zinter, B. J. Bormann, and R. Rothlein. 1999. Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion. J. Immunol. 163: 5173-5177.
44. Liu, G. 2001. Small molecule antagonists of the LFA-1/ICAM interaction as potential therapeutic agents. Exp. Opin. Ther. Pat. 11: 1383-1393.
45. Panzenbeck, M. J., D. D. Jeanfavre, T. A. Kelly, R. Lemieux, G. Nabozny, P. L. Reilly, and S. Desai. 2006. An orally active, primate selective antagonist of LFA-1 inhibits delayed-type hypersensitivity in a humanized-mouse model. Eur. J. Pharmacol. 534: 233-240.
46. Giblin, P. A., and R. M. Lemieux. 2006. LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics. Curr. Pharm. Des. 12: 2771-2795.
47. Wan, M. X., R. Schramm, D. Klintman, K. Welzenbach, G. Weitz-Schmidt, and H. Thorlacius. 2003. A statin-based inhibitor of lymphocyte function antigen-1 protects against ischemia/reperfusion-induced leukocyte adhesion in the colon. Br. J. Pharmacol. 140: 395-401.
48. Blazar, B. R., P. A. Taylor, A. Panoskaltsis-Mortari, G. S. Gray, and D. A. Vallera. 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: 2607-2618.
49. Yokota, A., N. Murata, O. Saiki, M. Shimizu, T. A. Springer, and T. Kishimoto. 1995. High avidity state of leukocyte function-associated antigen-1 on rheumatoid synovial fluid T lymphocytes. J. Immunol. 155: 4118-4124.
50. Hersmann, G. H., J. Kriegsmann, J. Simon, C. Hüttich, and R. Bräuer. 1998. Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis. Cell Adhes. Commun. 6: 69-82.
51. Genentech and XOMA discontinue efalizumab trial in rheumatoid arthritis. In Genentech Inc, XOMA Ltd. Genentech and XOMA Discontinue Rheumatoid Arthritis Trial. Media Release. 9, 2003.
52. Agarwal, S. K., and M. B. Brenner. 2006. Role of adhesion molecules in synovial inflammation. Curr. Opin. Rheumatol. 18: 268-276.
53. 4) and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis. Int. Immunol. 12: 141-150.
54. Haringman, J. J., D. M. Gerlag, T. J. Smeets, D. Baeten, F. van den Bosch, B. Bresnihan, F. C. Breedveld, H. J. Dinant, F. Legay, H. Gram, et al. 2006. A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum. 54: 2387-2392.
55. DiCesare, P., N. Hauser, D. Lehman, S. Pasumarti, and M. Paulsson. 1994. Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett. 354: 237-240. (Pubitemid 24335515)