Glucosaminylmuramyl dipeptide-induced changes in murine macrophage metabolism

The purpose of the study was to investigate influence of glucosaminyl muramyl dipeptide (GMDP) and its derivatives on adenosine deaminase (ADA, CE 3.5.4.4.) and 5'-nucleotidase (5-N, CE 3.1.3.5) activity in murine macrophages in vitro. The intensity of superoxide radicals (O2-) formation by these cells has been also studied. GMDP incubated with macrophages was found to inhibit substantially the activity of 5-N, without affecting the activity of ADA in these cells. The maximal effect on 5-N activity was noted following 24 h of co-culture and was accompanied by a higher intensity of O2- formation. GMDP added in doses ranging from 0.01 to 1 microgram/ml induced a gradual decrease in 5-N activity, with an increase in activity of the O2- -generating system. The GMDP analog with double dipeptide link GM(DP)2 has demonstrated the same activating effect as GMDP. The presence of dipeptide alanyl-D-isoglutamine in the GMDP structure is necessary for realization of the drug activating effect, as N-acetylglucosaminyl-N-acetylmuramyl failed to influence macrophage activity. Neither D-D nor L-L isomers of the drug affect the 5-N activity and O2- formation in macrophages. The mechanism of macrophages activation induced by GMDP may include the inhibition of 5-N activity and the stimulation in production of superoxide radicals.