Chemical structure required for immunoadjuvant and arthritogenic activities of cell wall peptidoglycans

Abstract

Water-soluble glycopeptides isolated from Lactobacillus plantarum cell walls by the use of Streptomyces L-3 enzyme were purified by gel filtration and ion-exchange column chromatography and were shown to be potently adjuvant-active and arthritogenic in the rat. Although these peptidoglycans contained non-peptidoglycan components (ribitol-teichoic acid and polysaccharide) attached to them in different proportions, the potency of both activities did not seem to be dependent upon the presence of these non-peptidoglycan components. Furthermore, the peptidoglycans of Staphylococcus epidermidis cell walls, which were essentially free from non-peptidoglycan components also showed potent immunoadjuvant and arthritogenic activities. These results indicated the importance of the peptidoglycan portion, but not of the non-peptidoglycan portion for both of these activities. Fractions containing peptidoglycans with an average glycan chain length of more than 5 disaccharide units were more potent than the peptidoglycan fractions with shorter glycan chains of 2–3 disaccharide units. Synthetic N- acetylmuramyl- l-alanyl- d-isoglutamine also exhibited an adjuvant activity as evaluated by its effect on the induction of experimental allergic encephalomyelitis in the PVG/c strain rat, although it was less active than the natural products with longer glycan chains. However, this synthetic compound failed to produce arthritis in the rat, suggesting that the minimal structure required for adjuvant activity is not sufficient for induction of adjuvant arthritis. A purified fraction with low ratio of peptide to glycan content seemed to be less potent in both arthritogenicity and immunoadjuvant activity despite the presence of an average glycan chain length of 8 disaccharide units. These findings suggest that polymerization of the minimal effective structure potentiates each of adjuvant and arthritogenic activities.