Differential effects of liposome-incorporation on liver macrophage activating potencies of rough lipopolysaccharide, lipid A, and muramyl dipeptide. Differences in susceptibility to lysosomal enzymes.

摘要: We investigated the in vitro activation of rat liver macrophages to a tumor-cytotoxic state with muramyl dipeptide (MDP), rough LPS (Re-LPS) and lipid A both free liposome-encapsulated form. The tumor cytotoxic was determined [methyl-3H]thymidine release assay using C26 colon adenocarcinoma cells as target cells. As shown previously, encapsulation MDP within multi-lamellar phospholipid vesicles greatly enhanced activating potency drug; by contrast, Re-LPS or significantly reduced compared form these agents. At dose 1 ng per ml significant induction cell lysis observed whereas maximal level obtained at concentration approximately 10 ng/ml. By liposomes diminished 20- 100-fold. minimal required induce detectable macrophage ng/ml, while did not any up 200 After 1-h pre-incubation lysosomal fraction from pH 4.8, macrophage-activating 95% remained fully active under conditions. conclude that, due endocytic uptake liposome-incorporated subsequent intralysosomal degradation, immunomodulators are inactivated respect their activate cytotoxicity.