The activation of tumoricidal properties in human blood monocytes by muramyl dipeptide requires specific intracellular interaction
Fogler, W.E.; Fidler, I.J.
Journal of Immunology 136(6): 2311-2317
1986
ISSN/ISBN: 0022-1767 PMID: 2936824 Document Number: 286115
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 moncytes 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 specifdic 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.