Abstract
A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), failed to produce polyarthritis with a wide dose range in a water-in-oil emulsion of mineral oil such as liquid paraffin, Drakeol, or heavy mineral oil. MDP, however, produced moderate to severe arthritis with almost 100% incidence in a water-in-oil emulsion made up of Difco incomplete adjuvant, which consists of Bavol F as an oil vehicle and Arlacel A as an emulsifier. N-acetylmuramyl-L-alanyl-L-isoglutamine did not produce arthritis, whereas 4,6-diacetyl-MDP produced the disease. Bacterial peptidoglycans, such as disaccharide peptides which were N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine and N-acetylglucosaminyl-6,o-acetyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine, also produced polyarthritis with low incidence in Difco oil but not in the other mineral oils described above. MDP and bacterial disaccharide peptides were able to produce the disease even in the latter mineral oil only when the concentration of Arlacel A was increased from 15% to 20 to 30% in the oil. We concluded that one of the minimal essential structures responsible for development of this disease is MDP, although the role of the oil vehicle remained uncertain, and there is no direct correlation between granulona formation and arthritogenicity of MDP.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adam A., Ciorbaru R., Petit J. F., Lederer E. Isolation and properties of a macromolecular, water-soluble, immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis. Proc Natl Acad Sci U S A. 1972 Apr;69(4):851–854. doi: 10.1073/pnas.69.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berry H., Willoughby D. A., Giroud J. P. Evidence for an endogenous antigen in the adjuvant arthritic rat. J Pathol. 1973 Dec;111(4):229–238. doi: 10.1002/path.1711110403. [DOI] [PubMed] [Google Scholar]
- Chang Y. H., Hoffman W. Adjuvant polyarthritis. III. Evidence in support of viral etiology. Arthritis Rheum. 1977 Nov-Dec;20(8):1507–1513. doi: 10.1002/art.1780200810. [DOI] [PubMed] [Google Scholar]
- Chedid L., Audibert F., Johnson A. G. Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents. Prog Allergy. 1978;25:63–105. [PubMed] [Google Scholar]
- Crowle A. J., Hu C. C. A comparison of n-hexadecane and mineral oil emulsions in induction of hypersensitivity in mice. Proc Soc Exp Biol Med. 1966 Oct;123(1):94–97. doi: 10.3181/00379727-123-31412. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- FISCHEL E. E., KABAT E. A., STOERK H. C., BEZER A. E. The role of tubercle bacilli in adjuvant emulsions on antibody production to egg albumin. J Immunol. 1952 Dec;69(6):611–618. [PubMed] [Google Scholar]
- Haley T. J., Farmer J., Jaques W. E., Frith C., Sprowls R. W., Schieferstein G. Dose-response hyperplasia and neoplasia from feeding N-2-fluorenylacetamide (2-FAA) to BALB/c mice for varying time intervals. Proc Soc Exp Biol Med. 1976 Jun;152(2):156–159. doi: 10.3181/00379727-152-39350. [DOI] [PubMed] [Google Scholar]
- Katayama T., Matsuda T., Kato K., Kotani S. Isolation and purification of D-alanyl-meso-2, 6-diaminopimelic acid endopeptidase of Streptomyces L-3 enzyme using soluble substrates of known chemical structure from Lactobacillus plantarum cell wall digests. Biken J. 1976 Sep;19(3):75–91. [PubMed] [Google Scholar]
- Koga T., Maeda K., Onoue K., Kato K., Kotani S. Chemical structure required for immunoadjuvant and arthritogenic activities of cell wall peptidoglycans. Mol Immunol. 1979 Mar;16(3):153–162. doi: 10.1016/0161-5890(79)90140-8. [DOI] [PubMed] [Google Scholar]
- Koga T., Pearson C. M., Narita T., Kotani S. Polyarthritis induced in the rat with cell walls from several bacteria and two Streptomyces species. Proc Soc Exp Biol Med. 1973 Jul;143(3):824–827. doi: 10.3181/00379727-143-37421. [DOI] [PubMed] [Google Scholar]
- Kohashi O., Kotani S., Shiba T., Ozawa A. Synergistic effect of polyriboinosinic acid:polyribocytidylic acid and either bacterial peptidoglycans or synthetic N-acetylmuramyl peptides on production of adjuvant-induced arthritis in rats. Infect Immun. 1979 Nov;26(2):690–697. doi: 10.1128/iai.26.2.690-697.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohashi O., Pearson C. M. Arthritogenicity of Mycobacterium smegmatis subfractions, related to different oil vehicle and different composition. Int Arch Allergy Appl Immunol. 1976;51(4):462–470. doi: 10.1159/000231620. [DOI] [PubMed] [Google Scholar]
- Kohashi O., Pearson C. M., Shimono T., Kotani S. Preparation of various fractions from Mycobacterium smegmatis, their arthritogenicity and their preventive effect on adjuvant disease. Int Arch Allergy Appl Immunol. 1976;51(4):451–461. doi: 10.1159/000231619. [DOI] [PubMed] [Google Scholar]
- Kohashi O., Pearson C. M., Watanabe Y., Kotani S., Koga T. Structural requirements for arthritogenicity of peptidoglycans from Staphylococcus aureus and Lactobacillus plant arum and analogous synthetic compounds. J Immunol. 1976 Jun;116(6):1635–1639. [PubMed] [Google Scholar]
- Kohashi O., Pearson C. M., Watanabe Y., Kotani S. Preparation of arthritogenic hydrosoluble peptidoglycans from both arthritogenic and non-arthritogenic bacterial cell walls. Infect Immun. 1977 Jun;16(3):861–866. doi: 10.1128/iai.16.3.861-866.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohasi O., Pearson C. M., Koga T. Arthritogenicity of wax D from various mycobacteria related to oil vehicle composition and to the combination with poly I:C, cord factor and acetylated wax D. Int Arch Allergy Appl Immunol. 1977;53(4):357–365. doi: 10.1159/000231772. [DOI] [PubMed] [Google Scholar]
- PEARSON C. M. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956 Jan;91(1):95–101. doi: 10.3181/00379727-91-22179. [DOI] [PubMed] [Google Scholar]
- PEARSON C. M., WOOD F. D. Studies of arthritis and other lesions induced in rats by the injection of mycobacterial adjuvant. VII. Pathologic details of the arthritis and spondylitis. Am J Pathol. 1963 Jan;42:73–95. [PMC free article] [PubMed] [Google Scholar]
- Stewart-Tull D. E., Shimono T., Kotani S., Kato M., Ogawa Y., Yamamura Y., Koga T., Pearson C. M. The adjuvant activity of a non-toxic, water-soluble glycopeptide present in large quantities in the culture filtrate of Mycobacterium tuberculosis strain DT. Immunology. 1975 Jul;29(1):1–15. [PMC free article] [PubMed] [Google Scholar]
- Stuewart-Tull D. E., Shimono T., Kotani S., Knights B. A. Immunosuppressive effect in mycobacterial adjuvant emulsions of mineral oils containing low molecular weight hydrocarbons. Int Arch Allergy Appl Immunol. 1976;52(1-4):118–128. doi: 10.1159/000231673. [DOI] [PubMed] [Google Scholar]
- Whitehouse M. W., Orr K. J., Beck F. W., Pearson C. M. Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology. 1974 Aug;27(2):311–330. [PMC free article] [PubMed] [Google Scholar]
- Wood F. D., Pearson C. M., Tanaka A. Capacity of mycobacterial wax D and its subfractions to induce adjuvant arthritis in rats. Int Arch Allergy Appl Immunol. 1969;35(5):456–467. doi: 10.1159/000230198. [DOI] [PubMed] [Google Scholar]
