Journal of Neuroimmunology
Volume 217, Issue 1 , Pages 65-73 , 10 December 2009

Autoantibodies to the δ-opioid receptor function as opioid agonists and display immunomodulatory activity

  • Parvathi Ranganathan

      Affiliations

    • Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, PO Box 245221, Tucson, Arizona 85724, USA
  • ,
  • Hao Chen

      Affiliations

    • Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, PO Box 245221, Tucson, Arizona 85724, USA
  • ,
  • Miranda K. Adelman

      Affiliations

    • Arizona Arthritis Center, University of Arizona, 1656 E. Mabel Street, PO Box 245221, Tucson, Arizona 85724, USA
  • ,
  • Samuel F. Schluter

      Affiliations

    • Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, PO Box 245221, Tucson, Arizona 85724, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 520 626 7013; fax: +1 520 626 2100.

Received 21 August 2009 ,Revised 7 October 2009 ,Accepted 9 October 2009.

References 

  1. Arumugam TV, Tang SC, Lathia JD, Cheng A, Mughal MR, Chigurupati S, et al. Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc. Natl. Acad. Sci. U. S. A. 2007;104:14104–14109
  2. Aukrust P, Froland SS, Liabakk NB, Muller F, Nordoy I, Haug C, et al. Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood. 1994;84:2136–2143
  3. Benard A, Boue J, Chapey E, Jaume M, Gomes B, Dietrich G. Delta opioid receptors mediate chemotaxis in bone marrow-derived dendritic cells. J. Neuroimmunol. 2008;197:21–28
  4. Bidlack JM. Detection and function of opioid receptors on cells from the immune system. Clin. Diagn. Lab. Immunol. 2000;7:719–723
  5. Blank M, Anafi L, Zandman-Goddard G, Krause I, Goldman S, Shalev E, et al. The efficacy of specific IVIG anti-idiotypic antibodies in antiphospholipid syndrome (APS): trophoblast invasiveness and APS animal model. Int. Immunol. 2007;19:857–865
  6. Bomsel M, Pastori C, Tudor D, Alberti C, Garcia S, Ferrari D, et al. Natural mucosal antibodies reactive with first extracellular loop of CCR5 inhibit HIV-1 transport across human epithelial cells. AIDS. 2007;21:13–22
  7. Bouhlal H, Hocini H, Quillent-Gregoire C, Donkova V, Rose S, Amara A, et al. Antibodies to C–C chemokine receptor 5 in normal human IgG block infection of macrophages and lymphocytes with primary R5-tropic strains of HIV-1. J. Immunol. 2001;166:7606–7611
  8. Bouhlal H, Latry V, Requena M, Aubry S, Kaveri SV, Kazatchkine MD, et al. Natural antibodies to CCR5 from breast milk block infection of macrophages and dendritic cells with primary R5-tropic HIV-1. J. Immunol. 2005;174:7202–7209
  9. Chen C, Li J, Bot G, Szabo I, Rogers TJ, Liu-Chen LY. Heterodimerization and cross-desensitization between the mu-opioid receptor and the chemokine CCR5 receptor. Eur. J. Pharmacol. 2004;483:175–186
  10. Dietrich G, Gaibelet G, Capeyrou R, Butour JL, Pontet F, Emorine LJ. Implication of the first and third extracellular loops of the mu-opioid receptor in the formation of the ligand binding site: a study using chimeric mu-opioid/angiotensin receptors. J. Neurochem. 1998;70:2106–2111
  11. Dussault N, Ducas E, Racine C, Jacques A, Pare I, Cote S, et al. Immunomodulation of human B cells following treatment with intravenous immunoglobulins involves increased phosphorylation of extracellular signal-regulated kinases 1 and 2. Int. Immunol. 2008;20:1369–1379
  12. Ephrem A, Chamat S, Miquel C, Fisson S, Mouthon L, Caligiuri G, et al. Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis. Blood. 2008;111:715–722
  13. Eslahpazir J, Jenabian MA, Bouhlal H, Hocini H, Carbonneil C, Gresenguet G, et al. Infection of macrophages and dendritic cells with primary R5-tropic human immunodeficiency virus type 1 inhibited by natural polyreactive anti-CCR5 antibodies purified from cervicovaginal secretions. Clin. Vaccine Immunol. 2008;15:872–884
  14. Fadhil I, Schmidt R, Walpole C, Carpenter KA. Exploring deltorphin II binding to the third extracellular loop of the delta-opioid receptor. J. Biol. Chem. 2004;279:21069–21077
  15. Finley MJ, Chen X, Bardi G, Davey P, Geller EB, Zhang L, et al. Bi-directional heterologous desensitization between the major HIV-1 co-receptor CXCR4 and the kappa-opioid receptor. J. Neuroimmunol. 2008;197:114–123
  16. Finley MJ, Happel CM, Kaminsky DE, Rogers TJ. Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell. Immunol. 2008;252:146–154
  17. Greeneltch KM, Kelly-Welch AE, Shi Y, Keegan AD. Chronic morphine treatment promotes specific Th2 cytokine production by murine T cells in vitro via a Fas/Fas ligand-dependent mechanism. J. Immunol. 2005;175:4999–5005
  18. Grimm MC, Ben-Baruch A, Taub DD, Howard OM, Resau JH, Wang JM, et al. Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization. J. Exp. Med. 1998;188:317–325
  19. Happel C, Steele AD, Finley MJ, Kutzler MA, Rogers TJ. DAMGO-induced expression of chemokines and chemokine receptors: the role of TGF-beta1. J. Leukoc. Biol. 2008;83:956–963
  20. Hartung HP. Advances in the understanding of the mechanism of action of IVIg. J. Neurol. 2008;255(Suppl 3):3–6
  21. Hebert TE. Opioid and chemokine receptor heterodimers: arranged marriages or dangerous liaisons?. Biochem. J. 2008;412:e7–e9
  22. Hereld D, Jin T. Slamming the DOR on chemokine receptor signaling: heterodimerization silences ligand-occupied CXCR4 and delta-opioid receptors. Eur. J. Immunol. 2008;38:334–337
  23. House RV, Thomas PT, Bhargava HN. A comparative study of immunomodulation produced by in vitro exposure to delta opioid receptor agonist peptides. Peptides. 1996;17:75–81
  24. Hurez V, Kaveri SV, Mouhoub A, Dietrich G, Mani JC, Klatzmann D, et al. Anti-CD4 activity of normal human immunoglobulin G for therapeutic use. (Intravenous immunoglobulin, IVIg). Ther. Immunol. 1994;1:269–277
  25. Jaume M, Laffont S, Chapey E, Blanpied C, Dietrich G. Opioid receptor blockade increases the number of lymphocytes without altering T cell response in draining lymph nodes in vivo. J. Neuroimmunol. 2007;188:95–102
  26. Kaveri S, Vassilev T, Hurez V, Lengagne R, Lefranc C, Cot S, et al. Antibodies to a conserved region of HLA class I molecules, capable of modulating CD8 T cell-mediated function, are present in pooled normal immunoglobulin for therapeutic use. J. Clin. Invest. 1996;97:865–869
  27. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N. Engl. J. Med. 2001;345:747–755
  28. Kessel A, Ammuri H, Peri R, Pavlotzky ER, Blank M, Shoenfeld Y, et al. Intravenous immunoglobulin therapy affects T regulatory cells by increasing their suppressive function. J. Immunol. 2007;179:5571–5575
  29. Li X, Varga EV, Stropova D, Zalewska T, Malatynska E, Knapp RJ, et al. delta-Opioid receptor: the third extracellular loop determines naltrindole selectivity. Eur. J. Pharmacol. 1996;300:R1–R2
  30. Mace G, Blanpied C, Emorine LJ, Druet P, Dietrich G. Isolation and characterization of natural human IgG with a morphine-like activity. Eur. J. Immunol. 1999;29:997–1003
  31. Mace G, Blanpied C, Emorine LJ, Druet P, Dietrich G. Morphine-like activity of natural human IgG autoantibodies is because of binding to the first and third extracellular loops of the mu-opioid receptor. J. Biol. Chem. 1999;274:20079–20082
  32. Mace G, Jaume M, Druet E, Blanpied C, Nguyen C, Druet P, et al. Identification of mu-opioid receptor epitopes recognized by agonistic IgG. Biochem. Biophys. Res. Commun. 2001;280:1142–1147
  33. Mace G, Jaume M, Blanpied C, Stephan L, Coudert JD, Druet P, et al. Anti-mu-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death. Blood. 2002;100:3261–3268
  34. Marchalonis JJ, Kaymaz H, Dedeoglu F, Schluter SF, Yocum DE, Edmundson AB. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain. Proc. Natl. Acad. Sci. U. S. A. 1992;89:3325–3329
  35. Mccarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend. 2001;62:111–123
  36. Mellon RD, Bayer BM. Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action. J. Neuroimmunol. 1998;83:19–28
  37. Miller B. delta opioid receptor expression is induced by concanavalin A in CD4+ T cells. J. Immunol. 1996;157:5324–5328
  38. Miyagi T, Chuang LF, Doi RH, Carlos MP, Torres JV, Chuang RY. Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes. J. Biol. Chem. 2000;275:31305–31310
  39. Navratilova E, Eaton MC, Stropova D, Varga EV, Vanderah TW, Roeske WR, et al. Morphine promotes phosphorylation of the human delta-opioid receptor at serine 363. Eur. J. Pharmacol. 2005;519:212–214
  40. Negi VS, Elluru S, Siberil S, Graff-Dubois S, Mouthon L, Kazatchkine MD, et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J. Clin. Immunol. 2007;27:233–245
  41. Nguyen K, Miller BC. CD28 costimulation induces delta opioid receptor expression during anti-CD3 activation of T cells. J. Immunol. 2002;168:4440–4445
  42. Pello OM, Martinez-Munoz L, Parrillas V, Serrano A, Rodriguez-Frade JM, Toro MJ, et al. Ligand stabilization of CXCR4/delta-opioid receptor heterodimers reveals a mechanism for immune response regulation. Eur. J. Immunol. 2008;38:537–549
  43. Peterson PK, Molitor TW, Chao CC. The opioid-cytokine connection. J. Neuroimmunol. 1998;83:63–69
  44. Prasad NK, Papoff G, Zeuner A, Bonnin E, Kazatchkine MD, Ruberti G, et al. Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes: a novel mechanism of action of IVIg involving the Fas apoptotic pathway. J. Immunol. 1998;161:3781–3790
  45. Quintana FJ, Cohen IR. The natural autoantibody repertoire and autoimmune disease. Biomed. Pharmacother. 2004;58:276–281
  46. Reipert BM, Stellamor MT, Poell M, Ilas J, Sasgary M, Reipert S, et al. Variation of anti-Fas antibodies in different lots of intravenous immunoglobulin. Vox Sang. 2008;94:334–341
  47. Rogers TJ, Steele AD, Howard OM, Oppenheim JJ. Bidirectional heterologous desensitization of opioid and chemokine receptors. Ann. N. Y. Acad. Sci. 2000;917:19–28
  48. Roy S, Wang J, Gupta S, Charboneau R, Loh HH, Barke RA. Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet. J. Neuroimmunol. 2004;147:78–81
  49. Roy S, Wang J, Kelschenbach J, Koodie L, Martin J. Modulation of immune function by morphine: implications for susceptibility to infection. J. Neuroimmune Pharmacol. 2006;1:77–89
  50. Salter RD, Howell DN, Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics. 1985;21:235–246
  51. Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science. 2001;291:484–486
  52. Seite JF, Shoenfeld Y, Youinou P, Hillion S. What is the contents of the magic draft IVIg?. Autoimmun Rev. 2008;7:435–439
  53. Shahabi NA, Mcallen K, Matta SG, Sharp BM. Expression of delta opioid receptors by splenocytes from SEB-treated mice and effects on phosphorylation of MAP kinase. Cell. Immunol. 2000;205:84–93
  54. Shahabi NA, Mcallen K, Sharp BM. Phosphorylation of activating transcription factor in murine splenocytes through delta opioid receptors. Cell. Immunol. 2003;221:122–127
  55. Shahabi NA, Mcallen K, Sharp BM. delta opioid receptors stimulate Akt-dependent phosphorylation of c-jun in T cells. J. Pharmacol. Exp. Ther. 2006;316:933–939
  56. Sharp BM. Opioid receptor expression and function. J. Neuroimmunol. 2004;147:3–5
  57. Sharp BM. Multiple opioid receptors on immune cells modulate intracellular signaling. Brain Behav. Immun. 2006;20:9–14
  58. Sharp BM, Gekker G, Li MD, Chao CC, Peterson PK. Delta-opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). Biochem. Pharmacol. 1998;56:289–292
  59. Sharp BM, Mckean DJ, Mcallen K, Shahabi NA. Signaling through delta opioid receptors on murine splenic T cells and stably transfected Jurkat cells. Ann. N. Y. Acad. Sci. 1998;840:420–424
  60. Sharp BM, Roy S, Bidlack JM. Evidence for opioid receptors on cells involved in host defense and the immune system. J. Neuroimmunol. 1998;83:45–56
  61. Sharp BM, Mcallen K, Gekker G, Shahabi NA, Peterson PK. Immunofluorescence detection of delta opioid receptors (DOR) on human peripheral blood CD4+ T cells and DOR-dependent suppression of HIV-1 expression. J. Immunol. 2001;167:1097–1102
  62. Shen H, Aeschlimann A, Reisch N, Gay RE, Simmen BR, Michel BA, et al. Kappa and delta opioid receptors are expressed but down-regulated in fibroblast-like synoviocytes of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 2005;52:1402–1410
  63. Shoenfeld Y, Toubi E. Protective autoantibodies: role in homeostasis, clinical importance, and therapeutic potential. Arthritis Rheum. 2005;52:2599–2606
  64. Shoenfeld Y, Rauova L, Gilburd B, Kvapil F, Goldberg I, Kopolovic J, et al. Efficacy of IVIG affinity-purified anti-double-stranded DNA anti-idiotypic antibodies in the treatment of an experimental murine model of systemic lupus erythematosus. Int. Immunol. 2002;14:1303–1311
  65. Steele AD, Szabo I, Bednar F, Rogers TJ. Interactions between opioid and chemokine receptors: heterologous desensitization. Cytokine Growth Factor Rev. 2002;13:209–222
  66. Steele AD, Henderson EE, Rogers TJ. Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication. Virology. 2003;309:99–107
  67. Suzuki S, Chuang LF, Yau P, Doi RH, Chuang RY. Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells. Exp. Cell Res. 2002;280:192–200
  68. Svenson M, Hansen MB, Ross C, Diamant M, Rieneck K, Nielsen H, et al. Antibody to granulocyte-macrophage colony-stimulating factor is a dominant anti-cytokine activity in human IgG preparations. Blood. 1998;91:2054–2061
  69. Szabo I, Wetzel MA, Zhang N, Steele AD, Kaminsky DE, Chen C, et al. Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization. J. Leukoc. Biol. 2003;74:1074–1082
  70. Tegeder I, Geisslinger G. Opioids as modulators of cell death and survival-unraveling mechanisms and revealing new indications. Pharmacol. Rev. 2004;56:351–369
  71. Vallejo R, De Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: a review. Am. J. Ther. 2004;11:354–365
  72. Vani J, Elluru S, Negi VS, Lacroix-Desmazes S, Kazatchkine MD, Bayary J, et al. Role of natural antibodies in immune homeostasis: IVIg perspective. Autoimmun. Rev. 2008;7:440–444
  73. Varga EV, Li X, Stropova D, Zalewska T, Landsman RS, Knapp RJ, et al. The third extracellular loop of the human delta-opioid receptor determines the selectivity of delta-opioid agonists. Mol. Pharmacol. 1996;50:1619–1624
  74. Varga EV, Rubenzik M, Grife V, Sugiyama M, Stropova D, Roeske WR, et al. Involvement of Raf-1 in chronic delta-opioid receptor agonist-mediated adenylyl cyclase superactivation. Eur. J. Pharmacol. 2002;451:101–102
  75. Varga EV, Navratilova E, Stropova D, Jambrosic J, Roeske WR, Yamamura HI. Agonist-specific regulation of the delta-opioid receptor. Life Sci. 2004;76:599–612
  76. Vassilev T, Gelin C, Kaveri SV, Zilber MT, Boumsell L, Kazatchkine MD. Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg). Clin. Exp. Immunol. 1993;92:369–372
  77. Vassilev TL, Kazatchkine MD, Van Huyen JP, Mekrache M, Bonnin E, Mani JC, et al. Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg). Blood. 1999;93:3624–3631
  78. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science. 1998;282:490–493
  79. Von Gunten S, Simon HU. Natural anti-Siglec autoantibodies mediate potential immunoregulatory mechanisms: implications for the clinical use of intravenous immunoglobulins (IVIg). Autoimmun. Rev. 2008;7:453–456
  80. Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol. Rev. 2001;81:299–343

PII: S0165-5728(09)00399-3

doi: 10.1016/j.jneuroim.2009.10.007

Journal of Neuroimmunology
Volume 217, Issue 1 , Pages 65-73 , 10 December 2009