Adjuvant Activities in Production of Reaginic Antibody by Bacterial Cell Wall Peptidoglycan or Synthetic N -Acetylmuramyl Dipeptides in Mice

Author:

Ohkuni Hisashi1,Norose Yoshihiko1,Ohta Midori1,Hayama Masaaki1,Kimura Yoshitami1,Tsujimoto Masaya2,Kotani Shozo2,Shiba Tetsuo3,Kusumoto Shoichi3,Yokogawa Kanae4,Kawata Shigeo4

Affiliation:

1. Department of Microbiology and Immunology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113, Japan

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

3. Faculty of Science, Osaka University, Toyonaka, Osaka 560, Japan

4. Research and Development Division, Dainippon Pharmaceutical Co., Suita, Osaka 564, Japan

Abstract

This paper is concerned with the adjuvant activity in stimulatory immunoglobulin E production against ovalbumin (OA) by bacterial cell walls, cell wall peptidoglycan (PG), and their PG fragments and synthetic N -acetylmuramyl (MurNAc) dipeptides in A/J mice. A PG isolated from Streptococcus pyogenes , PG subunit polymer and dimer obtained from Staphylococcus epidermidis , and water-soluble fragments of cell walls or PG prepared from Nocardia corynebacteriodes and Streptomyces gardneri were found to enhance both the primary and secondary responses of anti-OA immunoglobulin E antibody production. It was suggested that the PG portion, either intact or highly degraded, was capable of enhancing the immunoglobulin E antibody production, and there was no need for the non-PG moiety or intactness of PG structure for the adjuvant activity. This finding was confirmed and extended by the use of synthetic MurNAc dipeptides. Among eight MurNAc dipeptides tested, MurNAc- l -Ala- d -isoGln, MurNAc- l -Ala- d -Gln, MurNAc- l -Ala- d -Glu, and MurNAc- l -Ser- d -isoGln were found active as an adjuvant in the stimulation of the primary and secondary reaginic anti-OA antibody production in a similar way to the cell wall PG and their fragments. None of the synthetic MurNAc- l -Ala- l -isoGln, MurNAc- l -Ala- l -Gln, MurNAc- l -Ala- l -Glu, and MurNAc- l -Ala- d -isoAsn, on the other hand, stimulated the anti-OA immunoglobulin E antibody production in either primary or secondary response, indicating the importance for the adjuvancy in immunoglobulin E production of the configuration of the glutamic acid residues adjacent to the l -Ala (or l -Ser) in muramyl dipeptides.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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