Biochemical Evidence for Activation of Guinea Pig Macrophages by Muramyl Dipeptide

Glucose oxidation by macrophages isolated from (oil-induced) peritoneal exudate cells of guinea pigs was stimulated specifically by the synthetic immunological adjuvant, N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), when macrophages were cultured with it for 48 hr. The stimulation depended on the concentration of MDP: half maximal stimulation occurred with 0.05 pg MDP/ml (5>< 10" M). Analogs varying in the peptide moiety were examined for their effect and it was found that only adjuvant-active analogs were stimulatory. MDP was also found to stimulate [1"C]glucosamine incorporation into macrophages. Almost the same pattern of stimulation was observed in respect to time course, dose dependency and structureactivity relationship. These facts suggest that macrophages are target cells for MDP, and that MDP activates macrophages directly.