Comparative interaction of free and liposome-encapsulated nor-muramyl dipeptide or muramyl tripeptide phosphatidylethanolamine (3H-labelled) with human blood monocytes.
The purpose of this study was to analyse on biochemical and functional levels the interaction of free and liposome-encapsulated nor-muramyl dipeptide (nor-MDP) or muramyl tripeptide phosphatidylethanolamine (MTP-PE) with human peripheral blood monocytes. The activation of tumoricidal properties in monocytes by free MTP-PE required approximately 40-fold less material than free nor-MDP. Encapsulation of either MTP-PE or nor-MDP within multilamellar liposomes (MLV) increased the efficiency of the immunomodulators for activation of monocytes. The initial interaction of free 3H-nor-MDP or 3H-MTP-PE with monocytes was influenced by lipophilic derivatization, but neither derivatives exhibited characteristics of specific binding to the monocyte surface. The encapsulation of 3H-nor-MDP or 3H-MTP-PE within MLV increased uptake of both compounds by monocytes. The metabolic fate of MLV-entrapped 3H-nor-MDP was unaltered, but liposome encapsulation retarded the metabolism of 3H-MTP-PE. Collectively, the data suggest that the activation of monocytes by muramyl peptides results from an intracellular interaction which can be modulated by both lipophilic derivatization and/or liposome-encapsulation of this immunomodulator.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047676:N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine