α2-Macroglobulin binds CpG oligodeoxynucleotides and enhances their immunostimulatory properties by a receptor-dependent mechanism

Journal of Leukocyte Biology

Volumn 83, Issue 2, 2008, Pages 381-392

  Anderson, Ryan B ^a   Cianciolo, George J ^a   Kennedy, Margaret N ^a   Pizzo, Salvatore V ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Dendritic cells; LRP; TLR9; Vaccine adjuvant

Indexed keywords

ALPHA 2 MACROGLOBULIN; CPG OLIGODEOXYNUCLEOTIDE; TUMOR NECROSIS FACTOR ALPHA ANTIBODY;

ARTICLE; BIOLOGICAL ACTIVITY; CELL ACTIVATION; CYTOKINE PRODUCTION; HUMAN; HUMAN CELL; IMMUNOSTIMULATION; KINETICS; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN TRANSPORT;

ADJUVANTS, IMMUNOLOGIC; ALPHA-MACROGLOBULINS; ANIMALS; DNA; DRUG DELIVERY SYSTEMS; ENDOCYTOSIS; FEMALE; HUMANS; INTERFERON-ALPHA; INTERLEUKIN-6; LDL-RECEPTOR RELATED PROTEIN 1; LEUKOCYTE ELASTASE; LEUKOCYTES, MONONUCLEAR; LYMPHOCYTE ACTIVATION; MACROPHAGE ACTIVATION; MACROPHAGES, PERITONEAL; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NICKEL; TOLL-LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR-ALPHA;

MURINAE;

EID: 38949202945     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0407236     Document Type: Article

References (70)

1. Takeda, K., Kaisho, T., Akira, S. (2003) Toll-like receptors. Annu. Rev. Immunol. 21, 335-376.
2. Krieg, A. M., Yi, A. K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., Klinman, D. M. (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546-549.
3. Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K. A., Monks, B. G., Knetter, C. F., Lien, E., Nilsen, N. J., Espevik, T., Golenbock, D. T. (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. 5, 190-198.
4. Ahmad-Nejad, P., Hacker, H., Rutz, M., Bauer, S., Vabulas, R. M., Wagner, H. (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol. 32, 1958-1968.
5. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., Akira, S. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745.
6. Yi, A. K., Krieg, A. M. (1998) Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA. J. Immunol. 161, 4493-4497.
7. Bird, A. P. (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 8, 1499-1504.
8. Roman, M., Martin-Orozco, E., Goodman, J. S., Nguyen, M. D., Sato, Y., Ronaghy, A., Kornbluth, R. S., Richman, D. D., Carson, D. A., Raz, E. (1997) Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med. 3, 849-854.
9. Halpern, M. D., Kurlander, R. J., Pisetsky, D. S. (1996) Bacterial DNA induces murine interferon-γ production by stimulation of interleukin-12 and tumor necrosis factor-α. Cell. Immunol. 167, 72-78.
10. Krieg, A. M., Love-Homan, L., Yi, A. K., Harty, J. T. (1998) CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J. Immunol. 161, 2428-2434.
11. Elkins, K. L., Rhinehart-Jones, T. R., Stibitz, S., Conover, J. S., Klinman, D. M. (1999) Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. J. Immunol. 162, 2291-2298.
12. Zimmermann, S., Egeter, O., Hausmann, S., Lipford, G. B., Rocken, M., Wagner, H., Heeg, K. (1998) CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J. Immunol. 160, 3627-3630.
13. Alcon, V. L., Foldvari, M., Snider, M., Willson, P., Gomis, S., Hecker, R., Babiuk, L. A., Baca-Estrada, M. E. (2003) Induction of protective immunity in pigs after immunization with CpG oligodeoxynucleotides formulated in a lipid-based delivery system (Biphasix). Vaccine 21, 1811-1814.
14. Davis, H. L., Suparto, I. I., Weeratna, R. R., Jumintarto, Iskandriati, D. D., Chamzah, S. S., Ma'ruf, A. A., Nente, C. C., Pawitri, D. D., Krieg, A. M., Heriyanto, Smits, W., Sajuthi, D. D. (2000) CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans. Vaccine 18, 1920-1924.
15. Verthelyi, D., Kenney, R. T., Seder, R. A., Gam, A. A., Friedag, B., Klinman, D. M. (2002) CpG oligodeoxynucleotides as vaccine adjuvants in primates. J. Immunol. 168, 1659-1663.
16. Ballas, Z. K., Krieg, A. M., Warren, T., Rasmussen, W., Davis, H. L., Waldschmidt, M., Weiner, G. J. (2001) Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs. J. Immunol. 167, 4878-4886.
17. Carpentier, A. F., Chen, L., Maltonti, F., Delattre, J. Y. (1999) Oligodeoxynucleotides containing CpG motifs can induce rejection of a neuroblastoma in mice. Cancer Res. 59, 5429-5432.
18. Krieg, A. M. (2006) Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 5, 471-484.
19. Hartmann, G., Weiner, G. J., Krieg, A. M. (1999) CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc. Natl. Acad. Sci. USA 96, 9305-9310.
20. Sparwasser, T., Miethke, T., Lipford, G., Borschert, K., Hacker, H., Heeg, K., Wagner, H. (1997) Bacterial DNA causes septic shock. Nature 386, 336-337.
21. Monteith, D. K., Henry, S. P., Howard, R. B., Flournoy, S., Levin, A. A., Bennett, C. F., Crooke, S. T. (1997) Immune stimulation - a class effect of phosphorothioate oligodeoxynucleotides in rodents. Anticancer Drug Des. 12, 421-432.
22. Sparwasser, T., Hultner, L., Koch, E. S., Luz, A., Lipford, G. B., Wagner, H. (1999) Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. J. Immunol. 162, 2368-2374.
23. Lipford, G. B., Sparwasser, T., Zimmermann, S., Heeg, K., Wagner, H. (2000) CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses. J. Immunol. 165, 1228-1235.
24. Zhao, Q., Temsamani, J., Iadarola, P. L., Jiang, Z., Agrawal, S. (1996) Effect of different chemically modified oligodeoxynucleotides on immune stimulation. Biochem. Pharmacol. 51, 173-182.
25. Liang, H., Nishioka, Y., Reich, C. F., Pisetsky, D. S., Lipsky, P. E. (1996) Activation of human B cells by phosphorothioate oligodeoxynucleotides. J. Clin. Invest. 98, 1119-1129.
26. Sester, D. P., Naik, S., Beasley, S. J., Hume, D. A., Stacey, K. J. (2000) Phosphorothioate backbone modification modulates macrophage activation by CpG DNA. J. Immunol. 165, 4165-4173.
27. Krieg, A. M., Efler, S. M., Wittpoth, M., Al Adhami, M. J., Davis, H. L. (2004) Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27, 460-471.
28. Rockwell, P., O'Connor, W. J., King, K., Goldstein, N. I., Zhang, L. M., Stein, C. A. (1997) Cell-surface perturbations of the epidermal growth factor and vascular endothelial growth factor receptors by phosphorothioate oligodeoxynucleotides. Proc. Natl. Acad. Sci. USA 94, 6523-6528.
29. Bergan, R. C., Kyle, E., Connell, Y., Neckers, L. (1995) Inhibition of protein-tyrosine kinase activity in intact cells by the aptameric action of oligodeoxynucleotides. Antisense Res. Dev. 5, 33-38.
30. LaMarre, J., Wollenberg, G. K., Gonias, S. L., Hayes, M. A. (1991) Cytokine binding and clearance properties of proteinase-activated α 2-macroglobulins. Lab. Invest. 65, 3-14.
31. Colman, R. W. (2006) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, PA, USA, Lippincott Williams & Wilkins.
32. Chu, C. T., Pizzo, S. V. (1994) α 2-Macroglobulin, complement, and biologic defense: antigens, growth factors, microbial proteases, and receptor ligation. Lab. Invest. 71, 792-812.
33. Herz, J., Strickland, D. K. (2001) LRP: a multifunctional scavenger and signaling receptor. J. Clin. Invest. 108, 779-784.
34. Tobian, A. A., Harding, C. V., Canaday, D. H. (2005) Mycobacterium tuberculosis heat shock fusion protein enhances class I MHC crossprocessing and -presentation by B lymphocytes. J. Immunol. 174, 5209-5214.
35. Liao, H. X., Cianciolo, G. J., Staats, H. F., Scearce, R. M., Lapple, D. M., Stauffer, S. H., Thomasch, J. R., Pizzo, S. V., Montefiori, D. C., Hagen, M., Eldridge, J., Haynes, B. F. (2002) Increased immunogenicity of HIV envelope subunit complexed with α2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Vaccine 20, 2396-2403.
36. Cianciolo, G. J., Enghild, J. J., Pizzo, S. V. (2001) Covalent complexes of antigen and α(2)-macroglobulin: evidence for dramatically-increased immunogenicity. Vaccine 20, 554-562.
37. Hartmann, G., Weeratna, R. D., Ballas, Z. K., Payette, P., Blackwell, S., Suparto, I., Rasmussen, W. L., Waldschmidt, M., Sajuthi, D., Purcell, R. H., Davis, H. L., Krieg, A. M. (2000) Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. J. Immunol. 164, 1617-1624.
38. Vollmer, J., Weeratna, R., Payette, P., Jurk, M., Schetter, C., Laucht, M., Wader, T., Tluk, S., Liu, M., Davis, H. L., Krieg, A. M. (2004) Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur. J. Immunol. 34, 251-262.
39. Hartmann, G., Krug, A., Eigler, A., Moeller, J., Murphy, J., Albrecht, R., Endres, S. (1996) Specific suppression of human tumor necrosis factor- synthesis by antisense oligodeoxynucleotides. Antisense Nucleic Acid Drug Dev. 6, 291-299.
40. Sparwasser, T., Miethke, T., Lipford, G., Erdmann, A., Hacker, H., Heeg, K., Wagner, H. (1997) Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-α-mediated shock. Eur. J. Immunol. 27, 1671-1679.
41. Misra, U. K., Chu, C. T., Gawdi, G., Pizzo, S. V. (1994) Evidence for a second α 2-macroglobulin receptor. J. Biol. Chem. 269, 12541-12547.
42. Misra, U. K., Pizzo, S. V. (1999) Upregulation of macrophage plasma membrane and nuclear phospholipase D activity on ligation of the α2-macroglobulin signaling receptor: involvement of heterotrimeric and monomeric G proteins. Arch. Biochem. Biophys. 363, 68-80.
43. Takeshita, S., Takeshita, F., Haddad, D. E., Ishii, K. J., Klinman, D. M. (2000) CpG oligodeoxynucleotides induce murine macrophages to upregulate chemokine mRNA expression. Cell. Immunol. 206, 101-106.
44. Yasuda, K., Kawano, H., Yamane, I., Ogawa, Y., Yoshinaga, T., Nishikawa, M., Takakura, Y. (2004) Restricted cytokine production from mouse peritoneal macrophages in culture in spite of extensive uptake of plasmid DNA. Immunology 111, 282-290.
45. Imber, M. J., Pizzo, S. V. (1981) Clearance and binding of two electrophoretic "fast" forms of human α 2-macroglobulin. J. Biol. Chem. 256, 8134-8139.
46. Odom, A. R., Misra, U. K., Pizzo, S. V. (1997) Nickel inhibits binding of α2-macroglobulin-methylamine to the low-density lipoprotein receptor-related protein/α2-macroglobulin receptor but not the α2-macroglobulin signaling receptor. Biochemistry 36, 12395-12399.
47. Benimetskaya, L., Loike, J. D., Khaled, Z., Loike, G., Silverstein, S. C., Cao, L., el Khoury, J., Cai, T. Q., Stein, C. A. (1997) Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Nat. Med. 3, 414-420.
48. Bennett, R. M., Gabor, G. T., Merritt, M. M. (1985) DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA. J. Clin. Invest. 76, 2182-2190.
49. Bauer, S., Kirschning, C. J., Hacker, H., Redecke, V., Hausmann, S., Akira, S., Wagner, H., Lipford, G. B. (2001) Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA 98, 9237-9242.
50. Bauer, M., Heeg, K., Wagner, H., Lipford, G. B. (1999) DNA activates human immune cells through a CpG sequence-dependent manner. Immunology 97, 699-705.
51. Verthelyi, D., Ishii, K. J., Gursel, M., Takeshita, F., Klinman, D. M. (2001) Human peripheral blood cells differentially recognize and respond to two distinct CPG motifs. J. Immunol. 166, 2372-2377.
52. Krug, A., Rothenfusser, S., Hornung, V., Jahrsdorfer, B., Blackwell, S., Ballas, Z. K., Endres, S., Krieg, A. M., Hartmann, G. (2001) Identification of CpG oligonucleotide sequences with high induction of IFN-α/β in plasmacytoid dendritic cells. Eur. J. Immunol. 31, 2154-2163.
53. Iwasaki, A., Medzhitov, R. (2004) Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987-995.
54. Rykova, E. Y., Laktionov, P. P., Vlassov, V. V. (1999) Activation of spleen lymphocytes by plasmid DNA. Vaccine 17, 1193-1200.
55. Rykova, E. Yu, Pautova, L. V., Yakubov, L. A., Karamyshev, V. N., Vlassov, V. V. (1994) Serum immunoglobulins interact with oligonucleotides. FEBS Lett. 344, 96-98.
56. Srinivasan, S. K., Tewary, H. K., Iversen, P. L. (1995) Characterization of binding sites, extent of binding, and drug interactions of oligonucleotides with albumin. Antisense Res. Dev. 5, 131-139.
57. Britigan, B. E., Lewis, T. S., Waldschmidt, M., McCormick, M. L., Krieg, A. M. (2001) Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. J. Immunol. 167, 2921-2928.
58. Mulligan, P., White, N. R., Monteleone, G., Wang, P., Wilson, J. W., Ohtsuka, Y., Sanderson, I. R. (2006) Breast milk lactoferrin regulates gene expression by binding bacterial DNA CpG motifs but not genomic DNA promoters in model intestinal cells. Pediatr. Res. 59, 656-661.
59. Filion, M. C., Phillips, N. C. (1998) Major limitations in the use of cationic liposomes for DNA delivery. Int. J. Pharm. 162, 159-170.
60. Yasuda, K., Ogawa, Y., Kishimoto, M., Takagi, T., Hashida, M., Takakura, Y. (2002) Plasmid DNA activates murine macrophages to induce inflammatory cytokines in a CpG motif-independent manner by complex formation with cationic liposomes. Biochem. Biophys. Res. Commun. 293, 344-348.
61. Storni, T., Ruedl, C., Schwarz, K., Schwendener, R. A., Renner, W. A., Bachmann, M. F. (2004) Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J. Immunol. 172, 1777-1785.
62. Stein, C. A., Subasinghe, C., Shinozuka, K., Cohen, J. S. (1988) Physicochemical properties of phosphorothioate oligodeoxynucleotides. Nucleic Acids Res. 16, 3209-3221.
63. Pisetsky, D. S., Reich III, C. F. (1999) Influence of backbone chemistry on immune activation by synthetic oligonucleotides. Biochem. Pharmacol. 58, 1981-1988.
64. Gursel, M., Gursel, I., Mostowski, H. S., Klinman, D. M. (2006) CXCL16 influences the nature and specificity of CpG-induced immune activation. J. Immunol. 177, 1575-1580.
65. Hart, J. P., Gunn, M. D., Pizzo, S. V. (2004) A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens. J. Immunol. 172, 70-78.
66. Tighe, H., Takabayashi, K., Schwartz, D., Marsden, R., Beck, L., Corbeil, J., Richman, D. D., Eiden Jr., J. J., Spiegelberg, H. L., Raz, E. (2000) Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur. J. Immunol. 30, 1939-1947.
67. Rifkin, I. R., Leadbetter, E. A., Busconi, L., Viglianti, G., Marshak-Rothstein, A. (2005) Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol. Rev. 204, 27-42.
68. Gursel, M., Verthelyi, D., Gursel, I., Ishii, K. J., Klinman, D. M. (2002) Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide. J. Leukoc. Biol. 71, 813-820.
69. Zhao, Q., Matson, S., Herrera, C. J., Fisher, E., Yu, H., Krieg, A. M. (1993) Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides. Antisense Res. Dev. 3, 53-66.
70. Dalpke, A. H., Zimmermann, S., Albrecht, I., Heeg, K. (2002) Phosphodiester CpG oligonucleotides as adjuvants: polyguanosine runs enhance cellular uptake and improve immunostimulative activity of phosphodiester CpG oligonucleotides in vitro and in vivo. Immunology 106, 102-112.