The activation of human monocytes by liposome-encapsulated muramyl dipeptide analogues

G. Lopez-Berestein, K. Mehta, R. Mehta, R. L. Juliano, E. M. Hersh

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67 Scopus citations

Abstract

A growing body of evidence supports the concept of an important role for the monocyte-macrophage system in the suppression of neoplasia. Human or murine cells of the monocyte lineage can be activated by lymphokines, bacterial lipopolysaccharides (LPS), muramyl dipeptides (MDP), or by other signals to kill neoplastic cells while sparing normal ones. An important biochemical event apparently related to the enhanced cytotoxicity and microbicidal potential of activated macrophages is their increased ability to generate the superoxide anion (O2-) and hydrogen peroxide. Recently, findings from several laboratories indicated that liposomal encapsulation of macrophage activators, such as certain lymphokines or MDP, can markedly augment the ability of these substances to render rodent macrophages tumoricidal both in vitro and in vivo. These observations raise the possibility of using liposome-encapsulated macrophage activators to treat neoplasms in man. Several important questions remain to be answered, however, including whether the observations on rodent cells can be extended to human monocytes and the nature of the mechanisms underlying the augmented potency of liposome-encapsulated macrophage activators. We report herein the in vitro effects of a series of MDP derivatives on human peripheral blood monocytes, when these agents were presented in either free or liposome-encapsulated form. Several of the derivatives, especially lipophilic 6-0-stearoyl MDP, could prime human monocytes to increased superoxide production and to enhanced tumoricidal activity. Encapsulation of active MDP into liposomes resulted in an approximately 100-fold reduction in the concentration required to maximally activate monocytes. This may, in part, be explained by our observations that a radiolabeled MDP derivative is taken up much more effectively by human monocytes when presented in liposomal form rather than free form.

Original languageEnglish (US)
Pages (from-to)1500-1502
Number of pages3
JournalJournal of Immunology
Volume130
Issue number4
StatePublished - Dec 8 1983

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lopez-Berestein, G., Mehta, K., Mehta, R., Juliano, R. L., & Hersh, E. M. (1983). The activation of human monocytes by liposome-encapsulated muramyl dipeptide analogues. Journal of Immunology, 130(4), 1500-1502.