Augmentation by priming with interferon-gamma of the binding of a muramyl dipeptide derivative to macrophages resulting in synergistic macrophage activation.
Macrophage (MA) activation by recombinant murine interferon-gamma (rMuIFN-gamma) and a synthetic muramyl dipeptide derivative, N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)], was examined. The cytostatic activity of MA that had been primed with rMuIFN-gamma against Lewis lung adenocarcinoma cells was augmented extensively by exposure to MDP-Lys(L18) for a minimum of 15 min, though such treatment in the reverse sequence interfered with the effects of rMuIFN-gamma on MA. The binding assays revealed that rMuIFN-gamma bound to MA with an apparent dissociation constant (Kd) of 0.93 X 10(-9) M (16,000 binding molecules/cell), while MDP-Lys(L18) bound nonspecifically and was endocytosed by MA at 37 degrees. The amount of MDP-Lys(L18) bound to the rMuIFN-gamma-primed MA was significantly greater than that bound to the MA without rMuIFN-gamma priming. A small increase in the amount of MDP-Lys(L18) associated with MA was also observed at 4 degrees, but the amount was one order of magnitude less than that at 37 degrees. The binding of rMuIFN-gamma to MA was significantly suppressed by priming with MDP-Lys(L18). These results indicate that the binding of rMuIFN-gamma in preference to MDP-Lys(L18) to MA is of great importance in the mechanisms of MA activation.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism
D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; C036866:romurtide