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. 1980 Aug;40(4):557–564.

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.

K Yamamoto, M Kakinuma, K Kato, H Okuyama, I Azuma
PMCID: PMC1458118  PMID: 7000685

Abstract

Intravenous administration of 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) together with a specific antigen, PPD, in a water-in-oil emulsion was found to produce lung granuloma and to provide a low but significant grade of protection in mice against tuberculous infection within 4 weeks. However, these products, when given in an oil-in-water emulsion did not produce granuloma. Mycol-MDP alone produced comparable lung granuloma in both C57Bl/6 mice, high responders to BCG cell walls (CW), and C3H/He mice, low responders, 1 week after the injection, and when challenged at this time by aerosol containing virulent bovine tubercle bacilli, they showed significantly increased resistance. The present results confirmed the close relationship between lung granuloma and protection against aerosol challenge with Ravenel and revealed that the extent of lung granuloma at the time of aerosol challenge is crucial for the development of protection in mice immunized with mycol-MDP plus PPD as it is in mice immunized with BCG CW. However, these findings are not always the case for lung granuloma induced with mycol-MDP alone.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anacker R. L., Barclay W. R., Brehmer W., Larson C. L., Ribi E. Duration of immunity to tuberculosis in mice vaccinated intravenously with oil-treated cell walls of Mycobacterium bovis strain BCG. J Immunol. 1967 Jun;98(6):1265–1273. [PubMed] [Google Scholar]
  2. Azuma I., Sugimura K., Taniyama T., Yamawaki M., Yamamura Y. Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds. Infect Immun. 1976 Jul;14(1):18–27. doi: 10.1128/iai.14.1.18-27.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azuma I., Sugimura K., Yamamura Y., Kusumoto S., Tarumi Y. Adjuvant activity of synthetic cell-wall peptidoglycan subunits on monoazobenzenearsonate-N-acetyl-L-tyrosine and bacterial alpha-amylase in guinea pigs. Jpn J Microbiol. 1976 Feb;20(1):63–66. doi: 10.1111/j.1348-0421.1976.tb00909.x. [DOI] [PubMed] [Google Scholar]
  4. Barclay W. R., Anacker R., Brehmer W., Ribi E. Effects of oil-treated mycobacterial cell walls on the organs of mice. J Bacteriol. 1967 Nov;94(5):1736–1745. doi: 10.1128/jb.94.5.1736-1745.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chedid L., Parant M., Parant F., Lefrancher P., Choay J., Lederer E. 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 U S A. 1977 May;74(5):2089–2093. doi: 10.1073/pnas.74.5.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
  7. Emori K., Tanaka A. Granuloma formation by synthetic bacterial cell wall fragment: muramyl dipeptide. Infect Immun. 1978 Feb;19(2):613–620. doi: 10.1128/iai.19.2.613-620.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Igarashi T., Okada M., Azuma I., Yamamura Y. Adjuvant activity of synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds on cell-mediated cytotoxicity in syngeneic mice. Cell Immunol. 1977 Dec;34(2):270–278. doi: 10.1016/0008-8749(77)90249-0. [DOI] [PubMed] [Google Scholar]
  9. Kotani S., Kinoshita F., Morisaki I., Shimono T., Okunaga T., Takada H., Tsujimoto M., Watanabe Y., Kato K., Shiba T. Immunoadjuvant activities of synthetic 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with special reference to the effect of its administration with liposomes. Biken J. 1977 Dec;20(3-4):95–103. [PubMed] [Google Scholar]
  10. Kotani S., Watanabe Y., Kinoshita F., Shimono T., Morisaki I. Immunoadjuvant activities of synthetic N-acetyl-muramyl-peptides or -amino acids. Biken J. 1975 Jun;18(2):105–111. [PubMed] [Google Scholar]
  11. Ribi E., Anacker R. L., Barclay W. R., Brehmer W., Harris S. C., Leif W. R., Simmons J. Efficacy of mycobacterial cell walls as a vaccine against airborne tuberculosis in the Rheusus monkey. J Infect Dis. 1971 May;123(5):527–538. doi: 10.1093/infdis/123.5.527. [DOI] [PubMed] [Google Scholar]
  12. Yamamoto K., Karinuma M. Genetic control of granuloma response to oil-associated BCG cell wall vaccine in mice. Microbiol Immunol. 1978;22(6):335–348. doi: 10.1111/j.1348-0421.1978.tb00378.x. [DOI] [PubMed] [Google Scholar]

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