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. 1985 Feb;47(2):567–569. doi: 10.1128/iai.47.2.567-569.1985

Differential inhibition of macrophage microbicidal activity by liposomes.

M J Gilbreath, G M Swartz Jr, C R Alving, C A Nacy, D L Hoover, M S Meltzer
PMCID: PMC263210  PMID: 3967927

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J., Vickerman K. Fusion of host cell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana-infected macrophages. J Protozool. 1975 Nov;22(4):502–508. doi: 10.1111/j.1550-7408.1975.tb05219.x. [DOI] [PubMed] [Google Scholar]
  2. Alving C. R. Delivery of liposome-encapsulated drugs to macrophages. Pharmacol Ther. 1983;22(3):407–424. doi: 10.1016/0163-7258(83)90010-4. [DOI] [PubMed] [Google Scholar]
  3. Chang K. P., Dwyer D. M. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science. 1976 Aug 20;193(4254):678–680. doi: 10.1126/science.948742. [DOI] [PubMed] [Google Scholar]
  4. Hoover D. L., Nacy C. A. Analysis of macrophage interactions with cryopreserved amastigotes of Leishmania tropica. Infect Immun. 1983 Sep;41(3):1363–1367. doi: 10.1128/iai.41.3.1363-1367.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kleinerman E. S., Schroit A. J., Fogler W. E., Fidler I. J. Tumoricidal activity of human monocytes activated in vitro by free and liposome-encapsulated human lymphokines. J Clin Invest. 1983 Jul;72(1):304–315. doi: 10.1172/JCI110970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Meade C. J., Mertin J. Fatty acids and immunity. Adv Lipid Res. 1978;16:127–165. doi: 10.1016/b978-0-12-024916-9.50008-1. [DOI] [PubMed] [Google Scholar]
  7. Nacy C. A., Meltzer M. S., Leonard E. J., Wyler D. J. Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C3H/HeN mouse macrophages. J Immunol. 1981 Dec;127(6):2381–2386. [PubMed] [Google Scholar]
  8. Oster C. N., Nacy C. A. Macrophage activation to kill Leishmania tropica: kinetics of macrophage response to lymphokines that induce antimicrobial activities against amastigotes. J Immunol. 1984 Mar;132(3):1494–1500. [PubMed] [Google Scholar]
  9. Pagano R. E., Weinstein J. N. Interactions of liposomes with mammalian cells. Annu Rev Biophys Bioeng. 1978;7:435–468. doi: 10.1146/annurev.bb.07.060178.002251. [DOI] [PubMed] [Google Scholar]
  10. Poste G., Kirsh R., Fogler W. E., Fidler I. J. Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. Cancer Res. 1979 Mar;39(3):881–892. [PubMed] [Google Scholar]
  11. Ruco L. P., Meltzer M. S. Macrophage activation for tumor cytotoxicity: induction of tumoricidal macrophages by supernatants of PPD-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures. J Immunol. 1977 Sep;119(3):889–896. [PubMed] [Google Scholar]
  12. Schlager S. I., Meltzer M. S. Role of macrophage lipids in regulating tumoricidal activity. II. Internal genetic and external physiologic regulatory factors controlling macrophage tumor cytotoxicity also control characteristic lipid changes associated with tumoricidal cells. Cell Immunol. 1983 Aug;80(1):10–19. doi: 10.1016/0008-8749(83)90089-8. [DOI] [PubMed] [Google Scholar]
  13. Sone S., Fidler I. J. In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell Immunol. 1981 Jan 1;57(1):42–50. doi: 10.1016/0008-8749(81)90118-0. [DOI] [PubMed] [Google Scholar]

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