Activation of murine Kupffer cell tumoricidal activity by liposomes containing lipophilic muramyl dipeptide.
The ability of liposomes containing a lipophilic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine-glycerol dipalmitate, to induce Kupffer cell tumoricidal activity has been investigated. Liposomal N-acetylmuramyl-L-alanyl-D-isoglutamine-glycerol dipalmitate was 16-fold more potent than liposomal N-acetylmuramyl-L-alanyl-D-isoglutamine and 2,400-fold more potent than N-acetylmuramyl-L-alanyl-D-isoglutamine in inducing Kupffer cell tumoricidal activity in vitro. A single i.v. injection of liposomes containing N-acetylmuramyl-L-alanyl-D-isoglutamine-glycerol dipalmitate was capable of inducing Kupffer cell tumoricidal activity as measured against B16-melanoma cells after Kupffer cell isolation. Maximal cytotoxic activity was obtained with 1 microgram muramyl dipeptide-glycerol dipalmitate encapsulated within liposomes: doses of 10 or 100 micrograms inhibited tumoricidal activity. Kupffer cells from mice treated with liposomes containing N-acetylmuramyl-L-alanyl-D-isoglutamine-glycerol dipalmitate remained cytotoxic for at least 6 days after injection. Liposomal N-acetylmuramyl-L-alanyl-D-isoglutamine was significantly less potent than liposomal N-acetylmuramyl-L-alanyl-D-isoglutamine-glycerol dipalmitate in inducing Kupffer cell tumoricidal activity in situ. N-Acetylmuramyl-L-alanyl-D-isoglutamine was capable of inducing Kupffer cell tumoricidal activity in vitro: its failure to induce tumoricidal activity in situ at doses of 1,000 micrograms demonstrates the utility of liposomal carriers for the in vivo activation of Kupffer cells by muramyl dipeptides.
Phillips
N C
NC
McGill Centre for Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
Rioux
J
J
Tsao
M S
MS
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D000119:Acetylmuramyl-Alanyl-Isoglutamine