Correction of defective tumoricidal activity of macrophages from A/J mice by liposomal immunomodulators.
The ability of liposomal immunomodulators to restore abnormal macrophage tumoricidal activity has been studied. Macrophages from A/J mice have impaired responses in vitro to macrophage activating factor, gamma-interferon, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) or lipopolysaccharide when compared with macrophages from normoresponsive C57BL/6J mice. Liposomes containing a lipophilic muramyl dipeptide MDP-glyceroyl dipalmitate, macrophage activating factor or gamma-interferon restored tumoricidal activity to levels similar to C57BL/6J macrophages. Pretreatment of A/J mice with Corynebacterium parvum resulted in low levels of macrophage tumoricidal activity: treatment of C. parvum-induced A/J macrophages in vivo or in vitro with liposomal MDP-glyceroyl dipalmitate or liposomal macrophage activating factor resulted in normal levels of cytotoxicity. Macrophages from A/J mice were unable to phagocytose liposomes in vitro as rapidly or to the same extent as macrophages from C57BL/6J mice. The levels of cytotoxicity observed indicate that this is not a limiting factor for the induction of tumoricidal activity by liposomal immunomodulators.
Phillips
N C
NC
Montreal General Hospital Research Institute, Quebec, Canada.
Skamene
E
E
Chedid
L
L
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage*; D008264:Macrophages / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011425:Propionibacterium acnes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology*
D000276:Adjuvants, Immunologic; D008081:Liposomes