title: The activation of tumoricidal properties in human blood monocytes by muramyl dipeptide requires specific intracellular interaction.
abstract: The purpose of this study was to identify the mechanism by which muramyl dipeptide (MDP) activates antitumor cytotoxic properties in normal and interferon-gamma (IFN-gamma)-primed human peripheral blood monocytes. The structurally and functionally active MDP analog, nor-muramyl dipeptide (nor-MDP), and [3H]nor-MDP were used as reference glycopeptides. Direct activation of normal, noncytotoxic monocytes by nor-MDP was enhanced by its encapsulation within multilamellar vesicles (MLV). Studies with [3H]nor-MDP revealed that the activation of monocytes by nor-MDP was not attributable to its interaction with a specific cell surface receptor, nor did it result merely from the internalization by monocytes of glycopeptide. Subthreshold concentrations of nor-MDP could activate tumor cytotoxic properties in IFN-gamma-primed monocytes. The intracellular interaction of [3H]nor-MDP with IFN-gamma-primed monocytes was specific in that intracellular levels of radiolabeled material could be displaced and recovered as intact molecules by unlabeled nor-MDP, but not by a biologically inactive MDP stereoisomer. Collectively, these results suggest that the activation of tumoricidal properties in human blood monocytes by MDP occurs subsequent to intracellular interaction with specific MDP receptors.
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D001692:Biological Transport; D002451:Cell Compartmentation; D003593:Cytoplasm / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008081:Liposomes; D008262:Macrophage Activation; D009000:Monocytes / Q000276:immunology*; D011402:Pronase / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology; D017471:Receptors, Interferon
chemical_list: D008081:Liposomes; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D011402:Pronase