Skip to main content
SpringerLink
Log in

Muramyl Dipeptides: Prospect for Cancer Treatments and Immunostimulation

  • Chapter
Biological Response Modifiers in Human Oncology and Immunology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 166))

Abstract

It has been well established that bacterial cell walls, especially their peptidoglycan portions, exhibit a number of biological activities capable of modulating host defense mechanisms in various ways. Table 1 summarizes the activities detected by in vivo assays. The in vivo activities include the modulation (mainly potentiation) of antibody- and cell-mediated immune responses and the stimulation of reticuloendothelial system. These activities possibly relate to the other effects such as antigenspecific and nonspecific enhancement of host resistance to microbial infections and tumor development, and the induction of autoimmune diseases such as an experimental allergic encephalomyelitis with encephalitogenic antigens and “adjuvant” arthritis with or without foreign antigens. Other reported activities are concerned with the induction of a transient leukopenia, the following leukocytosis and the lasting monocytosis, the pyrogenicity, the induction of acute inflammatory reaction, epitheloid granulomas and recurrent multinodular lesions, the provocation of necrotic inflammation at the site prepared with tubercle bacilli, a transient decrease and the following increase of serum complement component levels, the promotion and inhibition of sleep, and others.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ellouz, F., A. Adam, R. Ciorbaru, and E. Lederer. 1974. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem. Biophys. Res. Commun. 59: 1317–1325.

    Article  PubMed  CAS  Google Scholar 

  2. Kotani, S., Y. Watanabe, F. Kinoshita, T. Shimono, I. Morisaki, T. Shiba, S. Kusumoto, Y. Tarumi, and K. Ikenaka. 1975. Immunoadjuvant activities of synthetic N-acetylmuramyl-peptides oramino acids. Biken J. 18: 105–111.

    PubMed  CAS  Google Scholar 

  3. Azuma, I., K. Sugimura, T. Taniyama, M. Yamawaki, Y. Yamamura, S. Kusumoto, S. Okada, and T. Shiba. 1976. Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic Nacetylmuramyl-dipeptide and the related compounds. Infect. Immun. 14: 18–27.

    PubMed  CAS  Google Scholar 

  4. Tanaka, A., R. Saito, K. Sugimura, I. Morisaki, S. Kotani, S. Kusumoto, and T. Shiba. 1977. Adjuvant activity of synthetic N-acetylmuramyl peptides in rats. Infect. Immun. 15: 131–136.

    Google Scholar 

  5. Souvannavong, V., A. Adam, and E. Lederer. 1978. Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetylmuramyl L-alanyl D-isoglutamine: comparison with Freund complete adjuvant. Infect. Immun. 19: 966–971.

    PubMed  CAS  Google Scholar 

  6. Heymer, B., H. Finger, and C.-H. Wirsing. 1978. Immunoadjuvant effects of the synthetic muramyl-dipeptide (MDP) N-acetylmuramyo L-alanyl-D-isoglutamine. Z. Immunitaetsforsch. 155: 87–92.

    CAS  Google Scholar 

  7. Leclerc, C., F. Audibert, and L. Chedid. 1978. Influence of a synthetic adjuvant (MDP) on qualitative and quantitative changes of serum globulins. Immunology 35: 963–970.

    PubMed  CAS  Google Scholar 

  8. Ohkuni, H., Y. Norose, M. Hayama, Y. Kimura, S. Kotani, T. Shiba, S. Kusumoto, K. Yokogawa, and S. Kawata. 1977. Adjuvant activities in production of reaginic antibody in mice of bacterial cell wall peptidoglycans or peptidoglycan subunits and of synthetic N-acetylmuramyl dipeptides. Biken J. 20: 131–136.

    PubMed  CAS  Google Scholar 

  9. Ohkuni, H., Y. Norose, M. Ohta, M. Hayama, Y. Kimura, M. Tsujimoto, S. Kotani, T. Shiba, S. Kusumoto, K. Yokogawa, and S. Kawata. 1979. Adjuvant activities in production of reaginic antibody by bacterial cell wall peptidoglycan or synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine. Infect. Immun. 24: 313–318.

    PubMed  CAS  Google Scholar 

  10. Löwy, I., C. Bona, and L. Chedid. 1977. Target cells for the activity of a synthetic adjuvant: muramyl dipeptide. Cell. Immunol. 29: 195–199.

    Article  PubMed  Google Scholar 

  11. Sugimoto, M., R. N. Germain, L. Chedid, and B. Benecerraf. 1978. Enhancement of carrier-specific helper T cell function by the synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP). J. Immunol. 120: 980–982.

    PubMed  CAS  Google Scholar 

  12. Löwy, I., J. Theze, and L. Chedid. 1980. Stimulation of the in vivo dinitrophanyl antibody response to the DNP conjugate of L-glutamic acid60-L-ananine30-L-tyrosinel0 (GAT) polymer by a synthetic adjuvant, muramyl dipeptide (MDP): target cells for adjuvant activity and isotypic pattern of MDP-stimulated response. J. Ímmunol. 124: 100–104.

    PubMed  Google Scholar 

  13. Masek, K., M. Zaoral, J. Jezek, and R. Straka. 1978. Immunoadjuvant activity of synthetic N-acetyl muramyl dipeptide. Experientia 34: 1363–1365.

    Article  PubMed  CAS  Google Scholar 

  14. Yamamura, Y., I. Azuma, K. Sugimura, M. Yamawaki, M. Uemiya, S. Okada, S. Okada, T. Shiba, and Y. Yamamura. 1978. Adjuvant activity of 6-O-mycoloyl derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutamine. Gann 67: 867–877.

    Google Scholar 

  15. Azuma, I., K. Sugimura, M. Yamawaki, M. Uemiya, S. Kusumoto, S. Okada, S. Okada, T. Shiba, and Y. Yamamura. 1978. Adjuvant activity of synthetic 6-O-“mycoloyl”-N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds. Infect. Immun. 20: 600–607.

    PubMed  CAS  Google Scholar 

  16. Uemiya, M., K. Sugimura, T. Kusama, I. Saiki, M. Yamawaki, I. Azuma, and Y. Yamamura. 1979. Adjuvant activity of 6-O-mycoloyl derivatives of M-acetyl-muramyl-L-alanyl-D-isogluta-mine and related compounds in mice and guinea pigs. Infect. Immun. 24: 83–89.

    PubMed  CAS  Google Scholar 

  17. Azuma, I., M. Yamawaki, M. Uemiya, I. Saiki, Y. Tanio, S. Kobayashi, T. Fukuda, I. Imada, and Y. Yamamura. 1979. Adjuvant and antitumor activities of quinonyl-N-acetyl muramyl di-peptides. Gann 70: 847–848.

    PubMed  CAS  Google Scholar 

  18. Saiki, I., Y. Tanio, M. Yamawaki, M. Uemiya, S. Kobayashi, T. Fukuda, H. Yukimasa, Y. Yamamura, and I. Azuma. 1981. Adjuvant activities of quinonyl-N-acetyl muramyl dipeptides in mice and guinea pigs. Infect. Immun. 31: 114–121.

    PubMed  CAS  Google Scholar 

  19. Matter, A. 1979. The effects of muramyldipeptide (MOP) in cell-mediated immunity. A comparison between in vitro and in vivo systems. Cancer Immunol. Immunother. 6: 201–210.

    Article  CAS  Google Scholar 

  20. Chedid, L., F. Audibert, P. Lefrancier, J. Choay, and E. Lederer. 1976. Modulation of the immune response by a synthetic adjuvant and analogs. Proc. Natl. Acad. Sci. USA 73: 2472–2475.

    Article  PubMed  CAS  Google Scholar 

  21. Leclerc, C., D. Juy, E. Bourgeois, and L. Chedid. 1979. In vivo regulation of humoral and cellular immune responses of mice by a synthetic adjuvant, N-acetyl-muramyl-L-alanyl-D-isoglutamine, muramyl dipeptide for MDP. Cell, Immunol. 45: 199–206.

    Article  CAS  Google Scholar 

  22. Souvannavong, V., and A. Adam. 1980. Opposite effects of the synthetic adjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine on the immune response in mice depending on experimental conditions. Eur. J. Immunol. 10: 654–656.

    Article  PubMed  CAS  Google Scholar 

  23. Kishimoto, T., Y. Hirai, K. Nakanishi, I. Azuma, A. Nagamatsu, and Y. Yamamura. 1979. Regulation of antibody response in different immunoglobulin classes. VI. Selective suppression of IgE response by administration of antigen-conjugated muramylpeptides. J. Immunol. 123: 2709–2715.

    PubMed  CAS  Google Scholar 

  24. Leclerc, C., E. Bouregois, and L. Chedid. 1982. Demonstration of muramyl dipeptide (MDP)-induced T suppressor cells responsible for MDP immunosuppressive activity. Eur. J. Immunol. 12: 249–252.

    Article  PubMed  CAS  Google Scholar 

  25. Siddiqui, W. A., D. W. Taylor, S. Kan, K. Kramer, S. M. Richmond-Crum, S. Kotani, T. Shiba, and S. Kusumoto. 1978. Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant. Science 201: 1237–1338.

    Article  PubMed  CAS  Google Scholar 

  26. Reese, R. T., W. Trager, J. B. Jensen, D. A. Miller, and R. Tantravehi. 1978. Immunization against malaria with antigen from Plasmodium falciparum cultivated in vitro. Proc. Natl. Acad. Sci. USA 75: 5665–5668.

    Article  PubMed  CAS  Google Scholar 

  27. Mitchell, W. H., G. Richards, A. Voller, F. M. Dietrich, and P. Dukor. 1979. Nor-MDP, saponin, corynebacteria, and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques. Bull. W. H. O. 57 (Suppl.l): 189–197.

    PubMed  Google Scholar 

  28. Siddiqui, W. A. 1982. Synthetic adjuvants and experimental human malaria vaccine, p. 245–249. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  29. Webster, R. G., W. P. Glezen, C. Hannoun, and W. G. Laver. 1977. Potentiation of the immune response to influenza virus subunit vaccines. J. Immunol. 119: 2073–2077.

    PubMed  CAS  Google Scholar 

  30. Okunaga, T. 1980. Potentiation of immune responses to influenza split virus vaccine by synthetic 6–0-acyl-muramylpeptides. J. Osaka Univ. Dent. Soc. 25: 29–52.

    CAS  Google Scholar 

  31. Woodard, L. F., N. M. Toone, and C. A. McLaughlin. 1980. Immunogenic properties of soluble antigens or whole cells of Brucella abortus strain 45/20 associated with immunoadjuvants. I. Soluble antigens. Can. J. Comp. Med. 44: 453–455.

    CAS  Google Scholar 

  32. Woodard, L. F., N. M. Toone, and C. A. McLaughlin. 1980. Immunogenic properties of soluble antigens or whole cells of Brucella abortus strain 45/20 associated with immunoadjuvants. II. Whole cells. Can. J. Comp. Med. 44: 456–458.

    CAS  Google Scholar 

  33. Woodard, L. F., N. M. Toone, and C. A. McLaughlin. 1980. Comparison of muramyl dipeptide, trehalose dimycolate, and dimethyl dioctadecyl ammonium bromide as adjuvants in Brucella abortus 45/20 vaccines. Infect. Immun. 30: 409–412.

    PubMed  CAS  Google Scholar 

  34. Langbeheim, H., R. Arnon, and M. Sela. 1978. Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies. Immunology 35: 573–579.

    PubMed  CAS  Google Scholar 

  35. Audibert, F., M. Jolivet, L. Chedid, J. E. Alouf, P. Boguet, P. Rivaille, and O. Siffert. 1981. Active antitoxic immunization by a diphtheria toxin synthetic oligopeptide. Nature 289: 593–594.

    Article  PubMed  CAS  Google Scholar 

  36. Audibert, F., and M. Jolivet. 1982. Immunization by a diphtheria toxin olibopeptide and MDP, a model for synthetic vaccines, p. 241–244. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and. T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  37. Chedid, L., and F. Audibert. 1982. Utilization of muramyl dipeptide derivatives as adjuvants of synthetic vaccines, p. 48–59. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  38. Binz, H., L. Tarcsay, H. Wigzell, and P. Dukor. 1981. Specific impaired alloreactivity of mice immunized with synthetic MLC T-lymphoblasts using muramylpeptides as adjuvant. Transplant. Proc. 13: 566–573.

    PubMed  CAS  Google Scholar 

  39. Tanaka, A., S. Nagao, R. Saito, S. Kotani, S. Kusumoto, and T. Shiba. 1977. Correlation of sterochemically specific structure in muramyl dipeptide between macrophage activation and adjuvant activity. Biochem. Biophys. Res. Commun. 77: 621–627.

    Article  PubMed  CAS  Google Scholar 

  40. Tanaka, A., S. Nagao, R. Saito, S. Kotani, S. Kusumoto, and T. Shiba. 1979. Stimulation of the reticuloendothelial system of mice by muramyl dipeptide. Infect. Immun. 24: 302–307.

    PubMed  CAS  Google Scholar 

  41. Waters, R. V., and R. W. Ferraresi. 1980. Muramyl dipeptide stimulation of particle clearance in several animal species. J. Reticuloendothel. Soc. 28: 457–471.

    PubMed  CAS  Google Scholar 

  42. Fraser-Smith, E. B., R. V. Waters, and T. R. Matthews. 1982. Correlation between in vivo anti-Pseudomonas and anti-Candida activities and clearance of carbon by the reticuloendothelial system for various muramyl dipeptide analogs, using normal and immunosuppressed mice. Infect. Immun. 35: 105–110.

    PubMed  CAS  Google Scholar 

  43. Kotani, S., Y. Watanabe, T. Shimono, K. Harada, T. Shiba, S. Kusumoto, K. Yokogawa, and M. Taniguchi. 1976. Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids. Biken J. 19: 9–13.

    PubMed  CAS  Google Scholar 

  44. Wuest, B., and E. D. Wachsmuth. 1982. Stimulatory effect of N-acetyl muramyl dipeptide in vivo: proliferation of bone marrow progenitor cells in mice. Infect. Immun. 37: 452–462.

    PubMed  CAS  Google Scholar 

  45. Kato, K., S. Kotani, K. Kawano, T. Monodane, H. Kitamura, S. Kusumoto, and T. Shiba. 1982. Monocytosis-inducing activity of L. monocytogenescell wall and muramyl dipeptides, p. 181–184. In Y, Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  46. Barot-Ciorbaru, R., J. Wietzerbin, J.-F. Petit, L. Chedid, E. Falcoff, and E. Lederer. 1978. Induction of interferon synthesis in mice by fractions from Nocardia. Infect. Immun. 19: 353–356.

    PubMed  CAS  Google Scholar 

  47. Barot-Ciorbaru, R., L. Catinot, J. Wietzerbin, J. -F Petit, L. Chedid, and E. Falcoff. 1981. Involvement of a radio re sistant cell in the production of circulating interferon induced by Nocardia fractions in mice. J. Reticuloendothel. Soc. 30: 247–257.

    PubMed  CAS  Google Scholar 

  48. Chedid, L., M. Parant, F. Parant, P. Lefrancier, J. Choay, and E. Lederer. 1977. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. Proc. Natl. Acad. Sci. USA 74: 2089–2093.

    Article  PubMed  CAS  Google Scholar 

  49. Parant, M., F. Parant, and L. Chedid. 1978. Enhancement of the neonate’s nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant. Proc. Natl. Acad. Sci. USA 75: 3395–3399.

    Article  PubMed  CAS  Google Scholar 

  50. Parant, M., C. Damais, F. Audibert, F. Parant, L. Chedid, E. Sache, P. Lefrancier, J. Choay, and E. Lederer. 1978. In vivo and in vitro stimulation of nonspecific immunity by the ß-D-p-aminophenyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglufamine and an oligomer prepared by cross-linking-With glutaraldehyde. J. Infect. Dis. 138: 378–386.

    Article  PubMed  CAS  Google Scholar 

  51. Chedid, L., M. Parant, F. Parant, F. Audibert, F. Lefrancier, J. Choay, and M. Sela. 1979. Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly (DL-alanine)-poly-(L-lysine) carrier. Proc. Natl. Acad. Sci. USA 76: 6557–6561.

    Article  PubMed  CAS  Google Scholar 

  52. Parant, M., G. Riveau, F. Parant, C. A. Dinarello, S. M. Wolff, and L. Chedid. 1980. Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide. J. Infect. Dis. 142: 708–715.

    Article  PubMed  CAS  Google Scholar 

  53. Parant, M. A., F. M. Audibert, L. A. Chedid, M. R. Level, P. L. Lefrancier, J. P. Choay, and E. Lederer. 1980. Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs. Infect. Immun. 27: 826–831.

    PubMed  CAS  Google Scholar 

  54. Audibert, F., M. Parant, C. Damais, P. Lefrancier, M. Derrien, J. Choay, and L. Chedid. 1980. Dissociation of immunostimulant activities of muramyl dipeptide (MDP) by linking amino-acids or peptides to the glutaminil residue. Biochem. Biophys. Res. Commun. 96: 915–923.

    Article  PubMed  CAS  Google Scholar 

  55. Lefrancier, P., M. Derrien, X. Jamet, J. Choay, E. Lederer, F. Audibert, M. Parant, F. Parant, and L. Chedid. Apyrogenic, adjuvant-active N-acetyl-muramyl-dipeptides. J. Med. Chem. 25: 87–90.

    Google Scholar 

  56. Chedid, L. A., M. A. Parant, F. M. Audibert, G. J. Riveau, F. J. Parant, E. Lederer, J. P. Choay, and P. L. Lefrancier. 1982. Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity. Infect. Immun. 35: 417–424.

    PubMed  CAS  Google Scholar 

  57. Finger, H., and C.-H Wirsing von Konig. 1980. Failure of synthetic muramyl dipeptide to increase antibacterial resistance. Infect. Immun. 27: 288–291.

    PubMed  CAS  Google Scholar 

  58. Humphres, R. C., P. R. Henika, R. W. Ferraresti, and J. L. Krhenbuhl. 1980. Effects of treatment with muramyl dipeptide and certain of its analogs on resistance to Listeria mono cytogenes in mice. Infect. Immun. 30: 462–466.

    PubMed  CAS  Google Scholar 

  59. Cummings, N. P., M. J. Pabst, and R. B. Johnston, Jr. 1980. Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide. J. Exp. Med. 152: 1659–1669.

    Article  PubMed  CAS  Google Scholar 

  60. Fraser-Smith, E. B., and T. R. Matthews. 1981. Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice. Infect. Immun. 34: 676–683.

    PubMed  CAS  Google Scholar 

  61. Matsumoto, K., H. Ogawa, O. Nagase, T. Kusama, and I. Azuma. 1981. Stimulation of nonspecific host resistance to infection induced by muramyl-dipeptides. Microbial. Immunol. 24: 1047–1058.

    Google Scholar 

  62. Matsumoto, K., H. Ogawa, T. Kusama, O. Nagase, N. Sawaki, M. Inage, S. Kusumoto, T. Shiba, and I. Azuma. 1981. Stimulation of nonspecific resistance to infection induced by 6–0acyl muramyl dipeptide analogs in mice. Infect. Immun. 32: 746–758.

    Google Scholar 

  63. Osada, Y., M. Mitsuyama, T. Une, K. Matsumoto, T. Otani, M. Satoh, H. Ogawa, and K. Nomoto. 1982. Effect of L18-MDP(Ala), a synthetic derivative of muramyl dipeptide, on nonspecific resistance of mice to microbial infections. Infect. Immun. 37: 292–300.

    PubMed  CAS  Google Scholar 

  64. Tanaka, A. 1982. Macrophage activation by muramyl dipeptide (MDP), p. 72–83. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  65. Kierszenbaum, and R. W. Ferraresi. 1979. Enhancement of host resistance against Trypanosoma cruzi infection by the immunoregulatory agent muramyl dipeptide. Infect. Immun. 25: 273–278.

    CAS  Google Scholar 

  66. Olds, G. R., L. Chedid, E. Lederer, and A. A. F. Mahmoud. 1980. Induction of resistance to Schistosoma mansoni by natural cord factor and synthetic lower homologues. J. Infect. Dis. 141: 473–478.

    Article  PubMed  CAS  Google Scholar 

  67. Krahenbuhl, J. L., S. D. Sharma, R. W. Ferraresi, and J. S. Remington. 1981. Effects of muramyl dipeptide treatment on resistance to infection with Toxoplasma gondii in mice. Infect. Immun. 31: 716–722.

    PubMed  CAS  Google Scholar 

  68. Azuma, I., and Y. Yamamura. 1979. Immunotherapy of cancer with BCG cell-wall skeleton and related materials. Gann Monograph Cancer Res. 24: 121–141.

    CAS  Google Scholar 

  69. Azuma, I., M. Uemiya, I. Saiki, M. Yamawaki, Y. Tanio, S. Kusumoto, T. Shiba, T. Kusama, K. Tobe, H. Ogawa, and Y. Yamamura. 1979. Synthetic immunoadjuvants-new immunotherapeutic agents. Dev. Immunol. 6: 311–330.

    CAS  Google Scholar 

  70. Yamamura, Y., K. Yasumoto, T. Ogura, and I. Azuma. 1981. Nocardía rubra-cell wall skeleton in the therapy of animal and human cancer, p. 71–90. In E. M. Hersh, M. A. Chirigos, and M. J. Mastrangelo (eds.), Augmentating agents in cancer immunity. Raven Press, New York.

    Google Scholar 

  71. Yamamura, Y., and I. Azuma. 1982. Cancer immunotherapy with cell-wall skeletons of BCG and Nocardia rubra and related synthetic compounds, p. 17–36. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  72. Ribi, E., C. A. McLaughlin, J. L. Cantrell, W. Brehmer, I. Azuma, Y. Yamamura, S. M. Strain, K. M. Hwang, and R. Toubiana. 1978. Immunotherapy for tumors with microbial constituents or their synthetic analogues, p. 131–154. In Staff of the University of Texas System Cancer Center (eds.), Immunotherapy of human cancer. Raven Press, New York.

    Google Scholar 

  73. Ribi, E., J. Cantrell, S. Schwartzman, and R. Parker. 1981. BCG cell wall skeleton, P3, MDP and other microbial components-structure activity studies in animal models, p. 15–31. In E. M. Hersh, M. A. Chirigos and M. J. Mastrangelo (eds.), Augmentating agents in cancer therapy. Raven Press, New York.

    Google Scholar 

  74. McLaughlin, S. M.. Schwartzman, B. L. Horner, G. H. Jones, J. G. Moffatt, J. J. Nestor, Jr., and D. Tedd. 1980. Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate. Science 208: 415–416.

    Article  PubMed  CAS  Google Scholar 

  75. Yarkoni, E., E. Lederer, and H. J. Rapp. 1981. Immunotherapy of experimental cancer with a mixture of synthetic muramyl di-peptide and trehalose dimycolate. Infect. Immun. 32: 273–276.

    PubMed  CAS  Google Scholar 

  76. Fidler, I. J., S. Sone, W. E. Fogler, and Z. L. Barnes. 1981. Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc. Natl. Acad. Sci. USA 78: 1680–1684.

    Article  PubMed  CAS  Google Scholar 

  77. Fidler, I. J. 1981. The in situ induction of tumoricidal activity in alveolar macrophages by liposomes containing muramyl dipeptide is a thymus-independent process. J. Immunol. 127: 1719–1720.

    PubMed  CAS  Google Scholar 

  78. Bruley-Rosset, M., I. Florentin, and G. Mathe. 1981. Macrophage activation by tufsin and muramyl-dipeptide. Mol. Cell. Biochem. 41: 113–118.

    Article  PubMed  CAS  Google Scholar 

  79. Sharma, S. D., V. Tsai, J. L. Krahenbuhl, and J. S. Remington. 1981. Augmentation of mouse natural killer cell activity.by muramyl dipeptide and its analogs. Cell. Immunol. 62: 101–109.

    Article  PubMed  CAS  Google Scholar 

  80. Nagai, Y., K. Akiyama, K. Suzuki, S. Kotani, Y. Watanabe, T. Shimono, T. Shiba, S. Kusumoto, F. Ikuta, and S. Takeda. 1978. Minimum structural requirements for encephalitogen and for adjuvant in the induction of experimental allergic encephalomyelitis. Cell. Immunol. 35: 158–167.

    Article  PubMed  CAS  Google Scholar 

  81. Nagai, Y., K. Akiyama, S. Kotani, Y. Watanabe, T. Shimono, T. Shiba, and S. Kusumoto. 1978. Structural specificity of synthetic peptide adjuvant for induction of experimental allergic encephalomyelitis. Cell. Immunol. 35: 168–172.

    Article  PubMed  CAS  Google Scholar 

  82. Koga, T., K. Maeda, K. Onoue, K. Kato, and S. Kotani. 1979. Chemical structure required for immunoadjuvant and arthritogenic activities of cell wall peptidoglycans. Mol. Immunol. 16: 153–162.

    Article  PubMed  CAS  Google Scholar 

  83. Maeda, K., T. Koga, S. Sakamoto, K. Onoue, S. Kotani, S. Kusumoto, T. Shiba, and A. Sumiyoshi. 1980. Structural requirement of synthetic N-acetyl-muramyl dipeptides for induction of experimental allergic encephalomyelitis in the rat. Microbiol. Immunol. 24: 771–776.

    PubMed  CAS  Google Scholar 

  84. Mitsuzawa, E., T. Yasuda, N. Tamura, and S. Ohtani. 1981. Experimental allergic encephalomyelitis induced by basic protein with synthetic adjuvant in comparison with Freund’s adjuvant. J. Neurol. Sci. 52: 133–145.

    Article  PubMed  CAS  Google Scholar 

  85. Kohashi, O., S. Kotani, T. Shiba, and A. Ozawa. 1979. Synergistic effect of polyriboinosinic acid:polyribocytidylic acid and either bacterial peptidoglycans or synthetic N-acetyl muramyl peptides on production of adjuvant-induced arthritis in rats. Infect. Immun. 26: 690–697.

    PubMed  CAS  Google Scholar 

  86. Koga, T., S. Sakamoto, K. Onoue, S. Kotani, and A. Sumiyoshi. 1980. Efficient induction of collagen arthritis by the use of a synthetic muramyl dipeptide. Arthritis Rheumat. 23: 993–997.

    Article  PubMed  CAS  Google Scholar 

  87. Nagao, S., and A. Tanaka. 1980. Muramyl dipeptide-induced adjuvant arthritis. Infect. Immun. 28: 624–626.

    PubMed  CAS  Google Scholar 

  88. Kohashí, O., A. Tanaka, S. Kotani, T. Shiba, S. Kusumoto, K. Yokogawa, S. Kawata, and A. Ozawa. 1980. Arthritis-inducing ability of a synthetic adjuvant, N-acetylmuramyl peptides, and bacterial disaccharide peptides related to different oil vehicles and their composition. Infect. Immun. 29: 70–75.

    PubMed  Google Scholar 

  89. Kohashi, O., C. M. Pearson, N. Tamaoki, A. Tanaka, K. Shímamura, A. Ozawa, S. Kotani, M. Saito, and K. Hioki. 1981. Role of thymus for N-acetyl muramyl-L-alanyl-D-isoglutamine-induced polyarhtritis and granuloma Tormation in euthymic and athymic nude rats or in neonatally thymectomized rats. Infect. Immun. 31: 758–766.

    PubMed  CAS  Google Scholar 

  90. Kohashi, O., Y. Kohashi, S. Kotani, and A. Ozawa. 1981. A new model of experimental arthritis induced by an aqueous form of synthetic adjuvant in immunodeficient rats (SHR and nude rats). Ryumachi 21 (Suppl.): 149–156.

    PubMed  Google Scholar 

  91. Zidek, Z., K. Masek, and Z. Jiricka. 1982. Arthritogenic activity of a synthetic immunoadjuvant, muramyl dipeptide. Infect. Immun. 35: 674–679.

    PubMed  CAS  Google Scholar 

  92. Kotani, S., Y. Watanabe, F. Kinoshita, K. Kato, K. Harada, T. Shiba, S. Kusumoto, Y. Tarumi, K. Ikenaka, S. Okada, S. Kawata, and K. Yokogawa. 1977. Gelation of the amoebocyte lysate of Tachypleus tridentatus by cell wall digest of several gram-positive bacteria and synthetic peptidoglycan subunits of natural and unnatural configurations. Biken J. 20: 5–10.

    PubMed  CAS  Google Scholar 

  93. Dinarello, C. A., R. J. Elín, L. Chedid, and S. M. Wolff. 1978. The pyrogenícity of the synthetic muramyl dipeptide and two structural analogues. J. Infect, Dis. 138: 760–767.

    Article  CAS  Google Scholar 

  94. Masek, K., O. Kadlecova, and P. Petrovicky. 1978. Pharmacological activity of bacterial peptidoglycan: the effect on temperature and sleep in the rat, p. 991–1003. In P. Rosenberd (ed.), Toxins: animal, plant and microbial. (Proceedings of the fifth international symposium). Pergamon Press, Oxford and New York.

    Google Scholar 

  95. Riveau, G., K. Masek. M. Parant, and L. Chedid. 1980. Central pyrogenic activity of muramyl peptide. J. Exp. Med. 152: 869–877.

    Article  PubMed  CAS  Google Scholar 

  96. Krueger, J. M., J. R. Pappenheimer, and M. L. Karnovsky. 1982. The composition of sleep-promoting factor isolated from human urine. J. Biol. Chem. 257: 1664–1669.

    PubMed  CAS  Google Scholar 

  97. Schwab, J. H. 1979. Acute and chronic inflammation induced by bacterial cell wall structures, p. 209–214. In D. Schlessinger (ed.), Microbiology 1979. American Society for Microbiology, Washington, D. C.

    Google Scholar 

  98. Emori, K., and A. Tanaka. 1978. Granuloma formation by synthetic bacterial cell wall fragment: muramyl dipeptide. Infect. Immun. 19: 613–620.

    PubMed  CAS  Google Scholar 

  99. Nagao, S., F. Ota, K. Emori, K. Inoue, and A. Tanaka. 1981. Epitheloid granuloma induced by muramyl dipeptide in immunologically deficient rats. Infect. Immun. 34: 993–999.

    PubMed  CAS  Google Scholar 

  100. Tanaka, A., K. Emori, S. Nagao, K. Koshima, O. Kohashi, M. Saitoh, and T. Kataoka. 1982. Epitheloid granuloma formation requiring no T-cell function. Am. J. Pathol. 106: 165–170.

    PubMed  CAS  Google Scholar 

  101. Ohkuni, H., and Y. Kimura. 1976. Increased capillary permeability in guinea pigs and rats by peptidoglycan fraction extracted from group A streptococcal cell walls. Exp. Cell. Biol. 44: 83–94.

    PubMed  CAS  Google Scholar 

  102. Nagao, S., Y. Iwata, and A. Tanaka. 1982. Extensive necrosis caused by the injection of MDP, p. 189–192. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  103. Lambris, J. S., J. B. Allen, and J. H. Schwab. 1982. In vivo changes in complement induced with peptidoglycan-polysaccharide polymers from streptococcal cell walls. Infect. Immun. 35: 377–380.

    PubMed  CAS  Google Scholar 

  104. Schwab, J. H., J. B. Allen, S. K. Anderle, F. Dalldorf, R. Eisenberg and W. J. Cromartie. 1982. Relationship of complement to experimental arthritis induced in rats with streptococcal cell walls. Immunology 46: 83–88.

    PubMed  CAS  Google Scholar 

  105. Audibert, F., B. Heymer, C. Gros, K. H. Schleifer, P. H. Seidl, and L. Chedid. 1978. Absence of binding of MDP, a synthetic immunoadjuvant to antipeptidoglycan antibodies. J. Immunol. 121: 1219–1222.

    PubMed  CAS  Google Scholar 

  106. Reichert, C. M., C. Carelli, M. Jolivet, F. Audibert, P. Lefrancier, and L. Chedid. Synthesis of coniugates containing N-acetylmuramyl-L-alanyl-D-isoglutaminyl (MDP). Their use as hapten-carrier systems. Mol. Immunol. 17: 357–363.

    Google Scholar 

  107. Bahr, G. M., F. Z. Modabber, G. A. W. Rook, M. L. Mehrotra, J. L. Stanford, and L. Chedid. 1982. Absence of antibodies to muramyl dipeptide in patients with tuberculosis or leprosy. Clin. Exp. Immunol. 47: 53–58.

    PubMed  CAS  Google Scholar 

  108. Bahr, G. M., C. Carelli, F. Audibert, F. Modabber, and L. Chedid. 1982. Analysis of the antigenic relationship of various derivatives of N-acetyl-muramyl-L-ala-D-isoglutamine (MDP), using anti-MDP antibodies. Mol. ÌmmunoT. 19: 737–745.

    Article  CAS  Google Scholar 

  109. Maeda, K., T. Koga, K. Onoue, S. Kotani, and A. Suumiyoshi. 1980. Induction of delayed type hypersensitivity-like skin reaction by peptidoglycans of bacterial cell walls. Microbiol. Immunol. 24: 335–348.

    PubMed  CAS  Google Scholar 

  110. Yamamota, K., M. Kakinuma, K. Kato, H. Okuyama, and I. Azuma. 1980. Relationship of anti-tuberculous protection to lung granuloma produced by intravenous injection of synthetic 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with or without specific antigens. Immunology 40: 557–564.

    Google Scholar 

  111. Hamamoto, Y., Y. Kobara, A. iKojima, Y. Kumazawa, and K. Yasuhira. 1981. Experimental production of pulmonary granulomas. I. Immune granulomas induced by chemically modified cell walls and their constituents. Br. J. Pathol. 62: 259–269.

    CAS  Google Scholar 

  112. Wachsmuth, E. D., and P. Dukor. 1982. Immunopathology of muramyl peptides, p. 60–71. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  113. Parant, M., F. Parant, L. Chedid, A. Yapo, J. F. Petit, and E. Lederer. 1979. Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse. Int. J. Immunopharmacol. 1: 35–41.

    Article  PubMed  CAS  Google Scholar 

  114. Tomasic, J., B. Ladesic Z. Valinger, and I. Hrsak. 1980. The metabolic fate of 14C-labeled peptidoglycan monomer in mice. I. Identification of the monomer and the corresponding pentapeptide in urine. Biochim. Biophys. Acta 629: 77–82.

    Article  PubMed  CAS  Google Scholar 

  115. Ladesic, B., J. Tomasic, S. Kveder, I. Hrsak. 1981. The metabolic fate of 14C-labeled immunoadjuvant peptidoglycan monomer. II. In vitro studies. Biochim. Biophys. Acta 678: 12–17.

    Article  PubMed  CAS  Google Scholar 

  116. Yapo, A., J. F. Petit, E. Lederer, M. Parant, F. Parant, and L. Chedid. 1982. Fate of two 14C labelled muramyl peptides: Ac-Mur-L-Ala-γ-D-Glu-meso-A2Pm and Ac-Mur-L-Ala-γ-D-Glu-meso-A2pm-D-Ala in mice. Evaluation of their ability tó increase nonspecific resistance to Klebsiella infection. Int. J. Immunopharmacol. 4: 143–149.

    Article  PubMed  CAS  Google Scholar 

  117. Valinger, Z., B. Ladesic, and J. Tomasic. 1982. Partial purification and characterization of N-acetylmuramyl-Lalanine amidase from human and mouse serum. Biochim. Biophys. Acta 701: 63–71.

    Article  PubMed  CAS  Google Scholar 

  118. Ogawa, T., S. Kotani, K. Fukuda, Y. Tsukamoto, M. Mori, S. Kusumoto, and T. Shiba. Stimulation of migration of human monocytes by bacterial cell walls and muramylpeptides. Infect. Immun. (submitted).

    Google Scholar 

  119. Ogawa, T., S. Kotani, S. Kusumoto, and T. Shiba. Possible chemotaxis of human monocyte by N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP. Infect. Immun. (submitted).

    Google Scholar 

  120. Tanaka, A., S. Nagao, K. Imai, and R. Mori. 1980. Macrophage activation by muramyl dipeptide as measured by macrophage spreading and attachment. Microbiol. Immunol. 24: 547–557.

    PubMed  CAS  Google Scholar 

  121. Nagao, S., T. Miki, and A. Tanaka. 1981. Macrophage activation by muramyl dipeptide (MOP) without lymphocyte participation. Microbiol. Immunol. 24: 41–50.

    Google Scholar 

  122. Pabst, M. J., and R. B. Johnson, Jr. 1980. Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide. J. Exp. Med. 151: 101–114.

    Article  PubMed  CAS  Google Scholar 

  123. Takada, H., M. Tsujimoto, K. Kao, S. Kotani, S. Kusumoto, M. Inage, T. Shiba, I. Yano, S. Kawata, and K. Yokogawa. 1979. Macrophage activation by bacterial cell walls and related synthetic compounds. Infect. Immun. 25: 48–52.

    PubMed  CAS  Google Scholar 

  124. Imai, K., M. Tomioka, S. Nagao, K. Kushima, and A. Tanaka. 1980. Biochemical evidence for activation of guinea pig macrophages by muramyl dipeptide. Biochem. Res. 25: 51–62.

    Google Scholar 

  125. Tanaka, A., S. Nagao, S. Ikegami, T. Shiba, and S. Kotani. 1982. The suppression of macrophage DNA synthesis by MDP, a possible correlate of macrophage activation, p. 201–204. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (ads.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  126. Imai, K., and A. Tanaka. 1981. Effect of muramyldipeptide, a synthetic bacterial adjuvant, on enzyme release from cultured mouse macrophages. Microbiol. Immunol. 25: 51–62

    PubMed  CAS  Google Scholar 

  127. Nichols, W. K., and F. H. Prosser. 1980. Induction of orni-thine decarboxylase in macrophages by bacterial lipopolysaccharide (LPS) and mycobacterial cell wall material. Life Sci. 27: 913–920.

    Article  PubMed  CAS  Google Scholar 

  128. Pabst, M. J., N. P. Cummings, T. Shiba, S. Kusumoto, and S. Kotani. 1980. Lipophilic derivative of muramyl dipeptide is more active than muramyl dipeptide in priming macrophages to release superoxide anion. Infect. Immun. 29: 617–622.

    PubMed  CAS  Google Scholar 

  129. Hadden, J. W. 1978. Effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage function in vitro. Can. Treat. Res. 62: 1981–1985.

    CAS  Google Scholar 

  130. Hadden, J. W., A. England, J. R. Sadlik, and E. M. Hadden. 1979. The comparative effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage proliferation and activation in vitro. Int. J. Immunopharmacol. 1: 17–27.

    Article  PubMed  CAS  Google Scholar 

  131. Takada, H., Y. Ishihara, S. Kotani, S. Kusumoto, T. Shiba, S. Kawata, and Y. Yokogawa. Macrophage activation by bacterial cell walls and related synthetic compounds. II. Phagocytosis stimulation. Microbiol. Immunol. (submitted).

    Google Scholar 

  132. Smialowicz, R. J., and J. H. Schwab. 1978. Inhibition of macrophage phagocytic activity by group A streptococcal cell walls. Infect. Immun. 20: 258–261.

    PubMed  CAS  Google Scholar 

  133. Nozawa, R. T., R. Sekiguchi, and T. Yokota. 1980. Stimulation by conditioned medium of L-929 fibroblasts, E. coli lipopoly saccharide, and muramyl dipeptide of candidacidal activity of mouse macrophages. Cell. Immunol. 53: 116–124.

    CAS  Google Scholar 

  134. Juy, D., and L. Chedid. 1975. Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants. Proc. Natl. Acad. Sci. USA 72: 4105–4109.

    Article  PubMed  CAS  Google Scholar 

  135. Taniyama, T., and H. T. Holden. 1979. Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. Cell. Immunol. 48: 369–374.

    Article  PubMed  CAS  Google Scholar 

  136. Galelli, A., Y. L. Garrec, L. Chedid, P. Lefrancier, M. Derrien, and M. Level. 1980. Macrophage stimulation in vitro by an inactive muramyl dipeptide derivative after conjugation to multi-poly (DL alanyl)-poly(L-lysine) carrier. Infect. Immun. 28: 1–5.

    PubMed  CAS  Google Scholar 

  137. Sone, S., and I. J. Fidler. 1980. Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. J. Immunol. 125: 2454–2460.

    PubMed  CAS  Google Scholar 

  138. Schroit, A. J., and I. J. Fidler. 1982. Effects of liposome. structure and lipid composition on the activation of tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res. 42: 161–167.

    PubMed  CAS  Google Scholar 

  139. Smialowicz, R. J., and J. H. Schwab. 1977. Cytotoxicity of rat macrophages activated by persistent or biodegradable bacterial cell walls. Infect. Immun. 17: 599–606.

    PubMed  CAS  Google Scholar 

  140. Akagawa, K. S., and T. Tokunaga. 1980. Effect of synthetic muramyl dipeptide (MDP) on differentiation of myeloid leukemic cells. Microbiol. Immunol. 24: 1005–1011.

    PubMed  CAS  Google Scholar 

  141. Yamamoto, Y., M. Tomida, M. Hozumi, and I. Azuma. 1981. Enhancement by immunostimulants of the production of mouse spleen cells of factor(s) stimulating differentiation of mouse myeloid leukemic cells. Gann 72: 828–833.

    PubMed  CAS  Google Scholar 

  142. Yamamoto, Y., S. Nagao, A. Tanaka, T. Koga, and K. Onoue. 1978. Inhibition of macrophage migration by synthetic muramyl dipeptide. Biochem. Biophys. Res. Commun. 80: 923–928.

    Article  PubMed  CAS  Google Scholar 

  143. Adam, A., V. Souvannavong, and E. Lederer. 1978. Nonspecific MIF-like activity induced by the synthetic immunoadjuvant: N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP). Biochim. Biophys. Res. Commun. 85: 684–690.

    Article  CAS  Google Scholar 

  144. Nagao, S., A. Tanaka, Y. Yamamoto, T. Koga, K. Onoue, T. Shiba, K. Kusumoto, and S. Kotani. 1979. Inhibition of macrophage migration by muramyl peptides. Infect. Immun. 24: 308–312.

    PubMed  CAS  Google Scholar 

  145. Homma, Y., K. Onozaki, T. Hashimoto, K. Miura, S. Nagao, and A. Tanaka. 1981. Different effect of (L)-fucose binding lectin on macrophage migration inhibition caused-by guinea pig migration inhibitory factor and synthetic muramyl dipeptide. Int. Arch. Aller. Appl. Immunol. 65: 27–33.

    Article  CAS  Google Scholar 

  146. Wahl, S. M., L. M. Wahl, J. B. McCarthy, L. Chedid, and S. M. Mergenhagen. 1979. Macrophage activation by mycobacterial water soluble components and synthetic muramyl dipeptide. J. Immunol. 122: 2226–2231.

    PubMed  CAS  Google Scholar 

  147. Oppenheim, J. J., A. Togawa, L. Chedid, and S. Mizel. 1980. Components of mycobactería and muramyl dipeptide with adjuvant activity induce lymphocyte activating factor. Cell. Immunol. 50: 71–81.

    Article  PubMed  CAS  Google Scholar 

  148. Tenu, J.-P., E. Lederer, and J.-F Petit. 1980. Stimulation of thymocyte mitogenic protein secretion and of cytostatic activity of mouse peritoneal macrophages by trehalose dimycolate and muramyl-dipeptide. Eur. J. Immunol. 10: 647–653.

    Article  PubMed  CAS  Google Scholar 

  149. Tribe, H., T. Koga, K. Onoue, S. Kotani, S. Kusumoto, and T. Shiba. 1981. Macrophage-stimulating effect of a synthetic muramyl dipeptide and its adjuvant-active and -inactive analogs for the production of T-cell activating monokines. Cell. Immunol. 64: 73–83.

    Article  Google Scholar 

  150. Tsukamoto, Y., W. Helsel, and S. M. Wahl. 1981. Macrophage production of fibronectin, a chemoattractant for fibroblasts. J. Immunol. 127: 673–678.

    PubMed  CAS  Google Scholar 

  151. Drapier, J.-C., G. Lemaire, and J.-F. Petit. 1982. Regulation of plasminogen activator secretion in mouse peritoneal macrophages. II. Inhibition by immunomodulators of bacterial origin. Int. J. Immunopharmacol. 4: 21–34.

    Article  PubMed  CAS  Google Scholar 

  152. Hamilton, J. A., J. B. Zabriskie, L. B. Laghman, and Y.-S. Chen. 1982. Streptococcal cell walls and synovial cell activation. Stimulation of synovial fibroblasts plasminogen activator activity by monocytes treated with group A streptococcal cell wall sonicates and muramyl dipeptide. J. Exp. Med. 155: 1702–1818.

    Article  PubMed  CAS  Google Scholar 

  153. Rutherford, B., K. Steffin, and J. Sexton. 1982. Activated human mononuclear phagocytes release a substance(s) that induced replication of quiescent human fibroblasts. J. Reticuloendothel. Soc. 31: 281–293.

    PubMed  CAS  Google Scholar 

  154. Damais, C., G. Riveau, M. Parant, J. Gerota, and L. Chedid. 1982. Production of lymphocyte activating factor in the absence of endogenous pyrogen by rabbit or human leukocytes stimulated by a muramyl dipeptide derivative. Int. J. Immunopharmacol. 4: 451–462.

    Article  PubMed  CAS  Google Scholar 

  155. Hotta, H., S. Hotta, H. Takada, and S. Kotani. Enhancement of Dengue-2 virus multiplication in cultured mouse peritoneal macrophages by bacterial cell walls and their related structural components. Infect. Immun. (submitted).

    Google Scholar 

  156. Igarashi, T., M. Okada, I. Azuma, and Y. Yamamura. 1977. Adjuvant activity of synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds on cell-mediated cytotoxicity in syngeneic mice. Cell. Immunol. 34: 270–278.

    Article  PubMed  CAS  Google Scholar 

  157. Takada, H., S. Kotani, S. Kusumoto, Y. Tarumi, K. Ikenaka, and T. Shiba. 1977. Mitogenic activity of adjuvant-active Nacetylmuramyl-L-alanyl-D-isoglutamine and its analogues. Biken J. 20: 81–85.

    PubMed  CAS  Google Scholar 

  158. Damais, C., M. Parant, and L. Chedid. 1977. Nonspecific activation of murine spleen cells in vitro by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine). Cell. Immunol. 34: 49–56.

    Article  PubMed  CAS  Google Scholar 

  159. Damais, C., M. Parant, L. Chedid, P. Lefrancier, and J. Choay. 1978. In vitro spleen cells responsiveness to various analogs of MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine), a synthetic immunoadjuvant, in MDP high-responder mice. Cell. Immunol. 35: 173–179.

    Article  PubMed  CAS  Google Scholar 

  160. Takada, H., M. Tsujimoto, S. Kotani, S. Kusumoto, M. Inage, T. Shiba, S. Nagao, I. Yano, S. Kawata, and K. Yokogawa. 1979. Mitogenic effects of bacterial cell walls, their fragments, and related synthetic compounds on thymocytes and splenocytes of guinea pigs. Infect. Immun. 25: 645–652.

    PubMed  CAS  Google Scholar 

  161. Takada, H., S. Nagao, S. Kotani, S. Kawata, K. Yokogawa, S. Kusumoto, T. Shiba, and I. Yano. 1980. Mitogenic effects of bacterial cell walls and their components on murine splenocytes. Biken J. 23: 61–68.

    PubMed  CAS  Google Scholar 

  162. Wood, D. D., and M. J. Straruch. 1981. Control of the mito-genicity of muramyl dipeptide. Int. J. Immunopharmacol. 3: 31–44.

    Article  PubMed  Google Scholar 

  163. Specter, S., H. Friedman, and L. Chedid. 1977. Dissociation between the adjuvant vs mitogenic activity of a synthetic muramyl dipeptide for murine splenocytes. Proc. Soc. Exp. Biol. Med. 155: 349–352.

    PubMed  CAS  Google Scholar 

  164. Specter, S., R. Cimprich, F. Friedman, and L. Chedid. 1978. Stimulation of an enhanced in vitro immune response by a synthetic adjuvant, muramyl dipeptide. J. Immunol. 120: 487–491.

    PubMed  CAS  Google Scholar 

  165. Leclerc, C., I. Lowy, and L. Chedid. 1978. Influence of MDP and of some analogous synthetic glycopeptides on the in vitro mouse spleen cell viability and immune response to sheep erythrocytes. Cell. Immunol. 38: 286–293.

    Article  PubMed  CAS  Google Scholar 

  166. Leclerc, C., E. Bourgeois, and L. Chedid. 1979. Enhancement by muramyl dipeptide of in vitro nude mice responses to a T-dependent antigen. Immunol. Commun. 8: 55–64.

    PubMed  CAS  Google Scholar 

  167. Lowy, I., and L. Chedid. 1979. Effect of cell division inhibitors on polyclonal activation can vary according to the target cell used. Immunol. Commun. 8: 479–494.

    PubMed  CAS  Google Scholar 

  168. Löwy, I., C. Leclerc, and L. Chedid. 1980. Induction of antibodies directed against self and altered-self determinants by synthetic adjuvant, muramyl dipeptide and some of its derivatives. Immunology 39: 441–450.

    PubMed  Google Scholar 

  169. Saito-Taki, T., M. J. Tanabe, H. Mochizuki, T. Matsumoto, M. Nakano, H. Takada, M. Tsujimoto, S. Kotani, S. Kusumoto, T. Shiba, K. Yokogawa, and S. Kawata. 1980. Polyclonal B cell activation by cell wall preparations of gram-positive bacteria. In vitro responses of spleen cells obtained from Balb/c, nu/nu. Nu/+, CH/He, C3H/HeJ and hybrid (CBA/NxBalb/c)Fl mice. Microbiol. Immunol. 24: 209–218.

    PubMed  CAS  Google Scholar 

  170. Lowy, I., C. Leclerc, B. Bourgeois, and L. Chedid. 1980. Inhibition of mitogen-induced polyclonal activation by a synthetic adjuvant, muramyl dipeptide (MDP). J. Immunol. 124: 320–325.

    PubMed  CAS  Google Scholar 

  171. Sugimura, K., M. Uemiya, I. Saiki, I. Azuma, and Y. Yamamura. 1979. The adjuvant activity of synthetic N-acetylmuramyl-dipeptide: evidence of initial target cells for the adjuvant activity. Cell. Immunol. 43: 137–149.

    Article  PubMed  CAS  Google Scholar 

  172. Leclerc, C., D. Juy, and L. Chedid. 1979. Inhibitory and stimulatory effects of a synthetic glycopeptide (MDP) on the in vitro PFC response: factors affecting the response. Cell. Immunol. 42: 336–343.

    Article  PubMed  CAS  Google Scholar 

  173. Watson, J., and C. Whitlock. 1978. Effect of a synthetic adjuvant on the induction of primary immune responses in T cell-depleted spleen cultures. J. Immunol. 121: 383–389.

    PubMed  CAS  Google Scholar 

  174. Azuma, I., T. Taniyama, K. Sugimura, A. A. Aladin, and Y. Yamamura. 1976. Mitogenic activity of the cell walls of mycobacteria, nocardia, corynebacteria and anaerobic coryneforms. Jpn. J. Microbiol. 20: 263–271.

    PubMed  CAS  Google Scholar 

  175. Azuma, I., K. Sugimura, M. Yamawaki, M. Uemiya, and Y. Yamamura. 1977. Mitogenic activity of cell-wall components in mouse spleen cells. Microbiol. Immunol. 21: 111–115.

    PubMed  CAS  Google Scholar 

  176. Sugimura, K., M. Uemiya, I. Azuma, M. Yamawaki, and Y. Yamamura. 1977. Macrophage dependency of T-lymphocyte mitogenesis by Nocardia rubra cell-wall skeleton. Microbiol. Immunol. 21: 525–530.

    PubMed  CAS  Google Scholar 

  177. Rasanan, L., and H. Arvilommi. 1981. Cell walls, peptidoglycans, and teichoic acids of gram-positive bacteria as poly-clonal inducers and immunomodulators of proliferative and lymphokine responses of human B and T lymphocytes. Infect. Immun. 34: 712–717.

    Google Scholar 

  178. Prunet, J., J. L. Birrien, J. Panijel, and P. Liacopoulos. 1978. On the mechanism of early recovery of specifically depleted lymphoid cell populations by nonspecific activation of T cells. Cell. Immunol. 37: 151–161.

    Article  PubMed  CAS  Google Scholar 

  179. Ishihara, Y., H. Takada, S. Kotani, S. Kusumoto, T. Shiba, S. Kawata, and K. Yokogawa. 1982. Stimulation of polymorphonuclear leukocytes by bacterial cell wall components and related synthetic compounds, p. 217–220. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  180. Jones, J. M., and J. H. Schwab. 1970. Effects of streptococcal cell wall fragments on lymphocytsosis and tissue culture cells. Infect. Immun. 1: 232–242.

    PubMed  CAS  Google Scholar 

  181. Musher, D. M., H. A. Verbrugh, and J. Verhoef. 1981. Suppression of phagocytosis and chemotaxis by cell wall components of Staphylococcus aureus. J. Immunol. 127: 84–88.

    PubMed  CAS  Google Scholar 

  182. Narita, T. 1974. Comparative studies on biological and immunological properties of bacterial and fungal cell walls, and solubilization and modification of active principle(s) by cell wall lytic enzymes. J. Osaka Univ. Dent. Soc. 19: 81–99. (In Japanese with English summary).

    Google Scholar 

  183. Staber, F. G., R. H. Gisler, G. Schumann, L. Tarcsay, E. Schlafli, and P. Dukor. 1978. Modulation of myelopoiesis by different bacterial cell-wall components: induction of colony-stimulating activity (by pure preparations, low-molecularweight degradation products, and a synthetic low-molecular analog of bacterial cell-wall components) in vitro. Cell. Immunol. 37: 174–187.

    Article  PubMed  CAS  Google Scholar 

  184. Ogawa, T., H. Takada, S. Kotani, S. Kusumoto, T. Shiba, S. Kawata, and K. Yokogawa. 1982. Basophile leukocyte stimulation by bacterial cell walls and related compounds, p. 221–224. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  185. Kimura, Y., Y. Norose, T. Kato, M. Furuya, M. Hida, Y. Banno, S. Kotani, S. Kusumoto, and T. Shiba. 1982. Histamine releasing activity from rat mast cells and platelets by peptidoglycan extracted from streptococcal cell walls and the related synthetic compounds, p. 225–228. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  186. Raskova, H., M. Ryc, J. Rotta, and K. Masek. 1971. Release of 5-hydroxy-tryptamine and morphological changes in blood platelets induced by mucopeptide of staphylococcal cell walls. J. Infect. Dis. 123: 587–594.

    Article  PubMed  CAS  Google Scholar 

  187. Ryc, M., and J. Rotta. 1975. The thrombocytolytic activity of bacterial peptidoglycans. Z. Inmiunitaetsforsch. 149 (Suppl.): 265–272.

    CAS  Google Scholar 

  188. Rotta, J., M. Ryc, K. Masek, and M. Zaoral. 1979. Biological activity of synthetic subunits of staphylococcus peptidoglycan. I. Pyrogenic and thrombocytolitic activity. Exp. Cell Biol. 47: 258–268.

    PubMed  CAS  Google Scholar 

  189. Harada, K., S. Kotani, H. Takada, M. Tsujimoto, Y. Hirachi, S. Kusumoto, T. Shiba, S. Kawata, K. Yokogawa, H. Nishimura, T. Kitaura, and T. Nakajima. 1982. Liberation of serotonin from rabbit blood platelets by bacterial cell walls and some related compounds, enzymatically prepared or synthesized. Infect. Immun. (in press).

    Google Scholar 

  190. Dewhirst, F. E. 1982. N-acetyl muramyl dipeptide stimulation of bone resorption in tissue culture. Infect. Immun. 35: 133–137.

    PubMed  CAS  Google Scholar 

  191. Bokisch, V. A. 1975. Interaction of peptidoglycans with anti-IgGs and with completment. Z. Immunitaetsforsch. 149 (Suppl.): 320–330.

    CAS  Google Scholar 

  192. Tauber, J. W., M. J. Polley, and J. B. Zabriskie. 1976. Nonspecific complement activation by streptococcal structures. II. Properdin-independent inhibition by alternative pathway. J. Exp. Med. 143: 1352–1366.

    Article  PubMed  CAS  Google Scholar 

  193. Greenblatt, J., R. J. Boackle, and J. H. Schwab. 1978. Activation of the alternative complement pathway by peptidoglycan from streptococcal cell well. Infect. Immun. 19: 296–303.

    PubMed  CAS  Google Scholar 

  194. Peperson, P. K., B. J. Wilkinson, Y. Kim, D. Schmeling, S. D. Douglas, P. G. Quie, and J. Verhoef. 1978. The key role of peptidoglycan in the opsonization of Staphylococcus aureus. J. Clin. Invest. 61: 597–609.

    Article  Google Scholar 

  195. Wilkinson, B. J., Y. Kim, and P. K. Peterson. 1981. Factors affecting complement activation by Staphylococcus aureus cell walls, their components, and mutants altered in teichoic acid. Infect. Immun. 32: 216–224.

    PubMed  CAS  Google Scholar 

  196. Kawasaki, A. 1982. Activation of human complement system by bacterial cell walls, their water-soluble enzymatic digests and related synthetic compounds. J. Osaka Univ. Dent. Soc. 27: 46–61. (In Japanese with English summary).

    Google Scholar 

  197. Kotani, S., H. Takada, M. Tsujimoto, T. Ogawa, K. Kato, T. Okunaga, Y. Ishihara, A. Kawasaki, I. Morisaki, N. Kono, T. Shimono, T. Shiba, S. Kusumoto, M. Inage, K. Harada, T. Kitaura, S. Kano, S. Inai, K. Nagai, M. Matsumoto, T. Kubo, M. Kato, Z. Tada, K. Yokogawa, and S. Kawata. 1981 Immunomodulating and related biological activities of bacterial cell walls and their components, enzymatically prepared or synthesized, p. 231–273. In H. Friedman, T. W. Klein and A. Szentivanyi (eds.), Immunomodulation by bacterial and their products. Plenum Press, New York.

    Chapter  Google Scholar 

  198. Ogawa, T., S. Kotani, M. Tsujimoto, S. Kusumoto, T. Shiba, S. Kawata, and K. Yokogawa. 1982. Contractile effects of bacterial cell walls, their enzymatic digests, and muramyl dipeptides on ileal strips from guinea pigs. Infect. Immun. 35: 612–619.

    PubMed  CAS  Google Scholar 

  199. Stewart-Tull, D. E. S., M. Davies, and D. M. Jackson. 1978. The binding of adjuvant-active mycobacterial peptidoglycans and glycopeptieds to mammalian membranes and their effect on artificial lipid bilayers. Immunology 34: 57–66.

    PubMed  CAS  Google Scholar 

  200. Shiba, T., S. Okada, S. Kusumoto, I. Azuma, and Y. Yamamura. 1978. Synthesis of 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with antitumor activity. Bull. Chem. Soc. Jpn. 51: 3307–3311.

    Article  CAS  Google Scholar 

  201. Kusumoto, S., M. Inage, T. Shiba, I. Azuma, and Y. Yamamura. 1978. Synthesis of long chain fatty acid esters of N-acetylmuramyl-L-alanyl-D-isoglutamine in relation to antitumor activity. Tetrandron Lett. 49: 4899–4902.

    Article  Google Scholar 

  202. Imada, I., I. Azuma, S. Kishimoto, Y. Yamamura, and H. Morimoto. 1972. The effect of ubiquinone-7 and its metabolites on the immune response. Int. Arch. Allerg. Appl. Immunol. 43: 898–907.

    Article  CAS  Google Scholar 

  203. Sugimura, K., I. Azuma, Y. Yamamura, I. Imada, M. Watanabe, and H. Morimoto. 1977. Effect of ubiquinone and related compounds on immune response, p. 151–163. In K. Folkers and Y. Yamamura (eds.), Biomedical and clinical aspects of coenzyme Q. Elseviers/North Holland Publishing Co., New York.

    Google Scholar 

  204. Imada, I., M. Watanabe, and H. Morimoto. 1978. Metabolism of ubiquinone, and biological activities of its metabolites and related compounds. Vitamins (Kyoto) 52: 493–501.

    CAS  Google Scholar 

  205. Brunner, K. T., J. Mauel, H. Rudolf, and B. Chapuis. 1970. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology 18: 501–515.

    PubMed  CAS  Google Scholar 

  206. Kotani, S., H. Takada, M. Tsujimoto, T. Kubo, T. Ogawa, I. Azuma, H. Ogawa, K. Matsumoto, W. A. Siddiqui, A. Tanaka, S. Nagao, O. Kohashi, S. Kanoy, T. Shiba, and S. Kusumoto. 1982. Nonspecific and antigen-specific stimulation of host defense mechanisms by lipophilic derivatives of muramyl dipeptides. In International colloquium on “bacteria and cancer” at Cologne, West Germany. Academic Press, London. (in press).

    Google Scholar 

  207. Tsujimoto, M. 1982. Fundamental studies to utilize the adjuvant activity of 6–0-acyl-muramyldipeptides to potentiate cellular and humoral immune responses for practical purpose. J. Osaka Univ. Dent. Soc. 26: 63–83.

    Google Scholar 

  208. Morisaki, I. 1980. Species and strain differences in responsiveness of laboratory animals to immunopotentiating activities of bacterial cell walls and their related adjuvants. J. Osaka Univ. Dent. Soc. 25: 229–249. (In Japanese with English summary).

    Google Scholar 

  209. Matsumoto, K., H. Ogawa, T. Kusama, and O. Nagase. 1982. Enhancement of nonspecific resistance to bacterial infection in mice induced by muramyl-dipeptide derivatives, p. 237–240. In Y. Yamamura, S. Kotani, I. Azuma, A. Koda and T. Shiba (eds.), Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, Amsterdam.

    Google Scholar 

  210. Matsumoto, K., T. Otani, T. Une, Y. Osada, H. Ogawa, and I. Azuma. Stimulation of nonspecific resistance to infection induced by MDP analogs substituted in the γ-carboxyl group, and evaluation of MDP-Lys(L18). Infect. Immun. (submitted).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Osaka University Dental School, Kita-ku, Osaka 530, Japan

    Shozo Kotani, Haruhiko Takada & Masachika Tsujimoto

  2. Institute of Immunological Science, Hokkaido University, Kita-15, Nishi-7, Kita-ku Sapporo 060, Japan

    Ichiro Azuma

  3. Osaka University, Yamadagami, Suita 565, Japan

    Yuichi Yamamura

Authors
  1. Shozo Kotani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ichiro Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haruhiko Takada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masachika Tsujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichi Yamamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of South Florida, Tampa, Florida, USA

    Thomas Klein , Steven Specter , Herman Friedman  & Andor Szentivanyi , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kotani, S., Azuma, I., Takada, H., Tsujimoto, M., Yamamura, Y. (1983). Muramyl Dipeptides: Prospect for Cancer Treatments and Immunostimulation. In: Klein, T., Specter, S., Friedman, H., Szentivanyi, A. (eds) Biological Response Modifiers in Human Oncology and Immunology. Advances in Experimental Medicine and Biology, vol 166. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1410-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-1410-4_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1412-8

  • Online ISBN: 978-1-4757-1410-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation