Marked enhancement of macrophage activation induced by synthetic muramyl dipeptide (MDP) conjugate using monoclonal anti-MDP antibodies.
Activation of peritoneal exudate macrophages of mice to inhibit the in vitro proliferation of tumor target cells was achieved with low concentrations of N-acetyl-L-alanyl-D-isoglutamine (MDP for muramyl dipeptide) conjugated to a synthetic carrier. Addition to the cultures of monoclonal anti-MDP or anti-carrier antibodies renders a thousandfold-smaller concentration of the conjugate highly effective in activating macrophages. This synergistic effect was observed neither with a control monoclonal antibody of different specificity nor with an F(ab)2 fragment of the monoclonal anti-MDP antibody. Other controls, such as addition to the cultures of the carrier alone with its specific monoclonal antibodies, also demonstrated that there exists a requirement for the presence of MDP in the conjugate. The possible uses of such a system as well as the underlying mechanisms are discussed.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002478:Cells, Cultured; D007140:Immunoglobulin Fab Fragments; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D000119:Acetylmuramyl-Alanyl-Isoglutamine