The macrophage, target cell of the synthetic adjuvant muramyl dipeptide.
The mechanism of adjuvant activity of the synthetic glycopeptide N-acetylmuramul-L-alanyl-D-isoglutamine or muramyl dipeptide (MDP) was studied using in vitro plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). Addition of MDP to DBA/2 mouse spleen cell cultures resulted regularly in a 2 to 3-fold increase of PFC numbers/10(6) recovered cells (p less than 0.01). Supernates (SPN) from MDP-stimulated cultures added to standard spleen cell + SRBC cultures brought about even more important increases of PFC numbers (p less than 0.01 to p less than 0.001). SPN from cultures supplemented with MDP alone (without SRBC) were more active than those of cell + MDP + SRBC cultures, and SPN removed on day 3 of culture were more active than those of day 5. This activity of SPN was maintained accross an H-2 histocompatibility barrier. Although pretreatment of spleen cells with anti-theta antigen serum entirely suppressed the anti-SRBC PFC response in spite of the presence of MDP, SPN from these cultures were as active as SPN from normal spleen cell MDP-stimulated cultures. In contrast, pretreatment of spleen cells with specific rabbit anti-mouse macrophage serum entirely suppressed both anti-SRBC response and SPN activity. It was concluded that the target cell for MDP is the macrophage which releases factors ultimately acting on B cells through T cell mediation.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000941:Antigens; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D006020:Glycopeptides / Q000494:pharmacology*; D006462:Hemolytic Plaque Technique; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009112:Muramic Acids / Q000138:chemical synthesis; D011135:Polysaccharides, Bacterial / Q000138:chemical synthesis; D012756:Sheep; D013154:Spleen / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D006020:Glycopeptides; D009112:Muramic Acids; D011135:Polysaccharides, Bacterial; D000119:Acetylmuramyl-Alanyl-Isoglutamine