This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Daemen, T. Articles by Scherphof, G. L. Search for Related Content PubMed PubMed Citation Articles by Daemen, T. Articles by Scherphof, G. L.

In Vitro Activation of Rat Liver Macrophages to Tumoricidal Activity by Free or Liposome-encapsulated Muramyl Dipeptide¹

Laboratory of Physiological Chemistry, University of Groningen, Bloemsingel 10, 9712 KZ Groningen, The Netherlands

We investigated the in vitro activation of rat liver macrophages to a tumoricidal state with free and liposome-encapsulated immunomodulators. The cytolytic activity of liver macrophages was determined by a radioactivity release assay using murine B16 melanoma cells, labeled with [methyl-³H]thymidine. Exposure of the liver macrophages to concentrations of 50 µg of free, nonencapsulated, muramyl dipeptide (MDP) per ml resulted in maximal levels of tumor cell lysis of approximately 20%. Encapsulation of the MDP within liposomes (multilamellar vesicles, 0.3 to 0.5 µm in diameter, consisting of egg phosphatidylcholine, cholesterol, and dicetylphosphate, 4:5:1) not only caused a 500-fold reduction in the amount of MDP required to obtain the same levels of cytolysis but also increased the maximally obtainable level of cytolysis more than 2-fold.

A synergistic effect of lipopolysaccharide and free or encapsulated MDP on cytolytic activity was observed when the macrophages were exposed to a combination of the two agents simultaneously.

Besides causing tumor cell lysis, activated macrophages were also able to suppress tumor cell proliferation by 80 to 90% as determined by a [methyl-³H]thymidine incorporation assay.

With a fixed amount of MDP, encapsulated in different amounts of liposomal lipid, the extent of macrophage activation was found to increase with a larger amount of encapsulating lipid. This increase in macrophage activation may be the result of a sustained intracellular release of encapsulated MDP from the liposomes. Liposome structure and composition will thus be important parameters in the in vivo application of liposomes as carriers of immunoactive substances.

¹ Research supported by the Dutch Foundation for Cancer Research, the Koningin Wilhelmina Fonds.

² To whom requests for reprints should be addressed.

Received 2/24/86. Revised 5/28/86. Accepted 5/30/86.

This article has been cited by other articles:

				S. Traub, S. von Aulock, T. Hartung, and C. Hermann Invited review: MDP and other muropeptides direct and synergistic effects on the immune system Innate Immunity, April 1, 2006; 12(2): 69 - 85. [Abstract] [PDF]

				J. A. A. M. Kamps, H. W. M. Morselt, P. J. Swart, D. K. F. Meijer, and G. L. Scherphof Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells PNAS, October 14, 1997; 94(21): 11681 - 11685. [Abstract] [Full Text] [PDF]