Abstract
Abstract: :
Purpose. Degradation of bacterial cell wall (BCW) components by serum enzymes is considered a key factor in reducing the apoptogenic and inflammatory activities of bacterial cell wall peptidoglycan and lipopolysaccharide (LPS). Methods. The degradation of the apoptogenic activity of bacterial cell wall peptidoglycan muramyl dipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine) and LPS by mouse, rat, rabbit, bovine, goat, monkey and human sera was assessed. Results. Degradation of synthetic MDP, but not LPS, apoptogenic activity was detected in all sera, but the levels/rate of degradation varied greatly between samples and against different synthetic MDP. Lipophilic MDP (i.e., N-acetylmuramyl-6-0-stearoyl-L-alanyl-D-glutamine amide) was not significantly degraded by any serum through 5 day incubation (consistent with lipophilic MDP’s in vivo toxicity). L,D-MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) and Deoxy-L,D-MDP [4-(2-acetamido-2-deoxy- ß-D-glucopyranosyl-N-acetylmuramyl-L-alanyl-D-glutamate amide] were degraded by all sera. Deoxy-L,D-MDP was more easily degraded by serum dipeptidase than L,D-MDP. Incremental loss of apoptogenic activity was associated with an incremental increase in free alanine in the MDP-serum sample, consistent with the degradation of MDP to muramic acid, L-alanine and D-isoglutamine and loss of biological activity. Conclusions. The results support serum degradation of BCW peptidoglycan, but indicate that BCW peptidoglycans containing -L-alanyl-D-isoglutamine may not be equally susceptible to degradation by different animal sera. Thus, serum dipeptidase resistant peptidoglycans of certain bacteria may be more often associated with experimental and natural disease such as arthritis, uveitis and glaucoma.
Keywords: bacterial disease • enzymes/enzyme inhibitors • pathology: human