Related Experiment Videos
Differential inhibition of macrophage microbicidal activity by liposomes
Abstract:
In vitro culture of murine resident peritoneal macrophages with lymphokine (LK)-rich leukocyte culture fluids induces enhanced microbicidal activity against amastigotes of the protozoan parasite Leishmania tropica. Macrophages infected with Leishmania and treated with LKs after infection acquire the capacity to kill the intracellular parasite within 72 h. When compared with control macrophage cultures treated with medium lacking LKs, 80 to 90% fewer macrophages treated with LKs contained amastigotes. In experiments designed to test liposome delivery of LKs to infected macrophages, addition of multilamellar liposomes composed of phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) completely abrogated LK-induced microbicidal activity. Liposomes containing only phosphatidylcholine were not inhibitory. Inhibition of LK activity by the liposomes occurred regardless of whether the liposomes contained LKs. Liposomal inhibition of activated macrophage effector activity was limited to intracellular killing; LK-induced macrophage extracellular cytolysis (i.e., tumor cytotoxicity) was not affected by liposome treatment. These data indicate that elucidation of the effects of liposome composition on acquired host defense mechanisms may be useful for the design of drug delivery systems that allow expression or augmentation of immunologically induced mechanisms for the intracellular destruction of infectious agents.
Insights
Lymphokines (LKs) enhance macrophage microbicidal activity against Leishmania tropica. However, specific liposomes containing phosphatidylserine inhibit this LK-induced intracellular killing, impacting drug delivery system design.
Area of Science:
- Immunology
- Parasitology
- Drug Delivery Systems
Background:
- Murine macrophages exhibit enhanced microbicidal activity against Leishmania tropica when cultured with lymphokines (LKs).
- LKs induce macrophages to acquire the capacity to kill intracellular Leishmania parasites within 72 hours.
- LK-treated macrophages show significantly reduced parasite burden compared to controls.
Purpose of the Study:
- To investigate the effect of liposome composition on lymphokine-induced macrophage microbicidal activity.
- To assess the potential of liposomes as drug delivery systems for augmenting host defense mechanisms.
Main Methods:
- In vitro culture of murine peritoneal macrophages.
- Treatment with lymphokine-rich leukocyte culture fluids.
- Assessment of microbicidal activity against Leishmania tropica amastigotes.
- Liposome preparation using phosphatidylcholine and phosphatidylserine (7:3 molar ratio) and phosphatidylcholine alone.
- Evaluation of liposome effects on LK-induced intracellular killing and extracellular cytotoxicity.
Main Results:
- Liposomes composed of phosphatidylcholine and phosphatidylserine abrogated LK-induced microbicidal activity against intracellular Leishmania.
- Liposomes containing only phosphatidylcholine did not inhibit LK activity.
- Liposomal inhibition was observed irrespective of whether LKs were encapsulated within the liposomes.
- Liposomes specifically inhibited intracellular killing, not LK-induced macrophage extracellular cytotoxicity (tumor cytotoxicity).
Conclusions:
- Liposome composition significantly influences the efficacy of immunologically induced host defense mechanisms.
- Specific liposomal formulations can inhibit lymphokine-mediated intracellular parasite destruction.
- Understanding these interactions is crucial for designing effective drug delivery systems for infectious agents.