The activation of tumoricidal properties in macrophages of endotoxin responder and nonresponder mice by liposome-encapsulated immunomodulators

W. E. Fogler, James E Talmadge, I. J. Fidler

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Abstract

The purpose of these studies was to determine whether various immunomodulators such as lipopolysaccharide (LPS), lymphokines with macrophage activation factor (MAF), or muramyl dipeptide (MDP) could activate the tumoricidal properties in LPS-responsive C3H/HeN and LPS-unresponsive C3H/HeJ mice. In all studies we examined the interaction of the different immunomodulators in a free form or encapsulated within liposomes (multilamellar vesicles) with alveolar macrophages (AM) and/or peritoneal exudate macrophages (PEM). In vivo infection with viable Mycobacterium bovis, strain BCG, induced the development of highly activated macrophages from C3H/HeN mice, yet only marginally activated macrophages from C3H/HeJ mice. In vitro incubation with MAF or LPS rendered AM and PEM from C3H/HeN, but not C3H/HeJ, mice tumoricidal. The failure of C3H/HeJ macrophages to respond to LPS stimulation was due to an intracellular defect. C3H/HeJ macrophages bound fluorescein-conjugated LPS to the same extent as that found for C3H/HeN macrophages. Furthermore, LPS encapsulated in liposomes activated C3H/HeN but not C3H/HeJ AM and/or PEM. Macrophages from both strains could be rendered highly tumoricidal following interaction with free MDP or following endocytosis of liposomes containing MDP or MAF. These results indicate that the inability of C3H/HeJ macrophages to respond to LPS stimulation is specific and that the activation of macrophages by different immunomodulators could occur by different pathways.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalRES Journal of the Reticuloendothelial Society
Volume33
Issue number3
StatePublished - Jan 1 1983

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Immunologic Factors
Endotoxins
Liposomes
Lipopolysaccharides
Macrophages
Macrophage Activation
Inbred C3H Mouse
Acetylmuramyl-Alanyl-Isoglutamine
Alveolar Macrophages
Peritoneal Macrophages
Exudates and Transudates
Mycobacterium bovis
Lymphokines
Endocytosis
Fluorescein
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "The activation of tumoricidal properties in macrophages of endotoxin responder and nonresponder mice by liposome-encapsulated immunomodulators",
abstract = "The purpose of these studies was to determine whether various immunomodulators such as lipopolysaccharide (LPS), lymphokines with macrophage activation factor (MAF), or muramyl dipeptide (MDP) could activate the tumoricidal properties in LPS-responsive C3H/HeN and LPS-unresponsive C3H/HeJ mice. In all studies we examined the interaction of the different immunomodulators in a free form or encapsulated within liposomes (multilamellar vesicles) with alveolar macrophages (AM) and/or peritoneal exudate macrophages (PEM). In vivo infection with viable Mycobacterium bovis, strain BCG, induced the development of highly activated macrophages from C3H/HeN mice, yet only marginally activated macrophages from C3H/HeJ mice. In vitro incubation with MAF or LPS rendered AM and PEM from C3H/HeN, but not C3H/HeJ, mice tumoricidal. The failure of C3H/HeJ macrophages to respond to LPS stimulation was due to an intracellular defect. C3H/HeJ macrophages bound fluorescein-conjugated LPS to the same extent as that found for C3H/HeN macrophages. Furthermore, LPS encapsulated in liposomes activated C3H/HeN but not C3H/HeJ AM and/or PEM. Macrophages from both strains could be rendered highly tumoricidal following interaction with free MDP or following endocytosis of liposomes containing MDP or MAF. These results indicate that the inability of C3H/HeJ macrophages to respond to LPS stimulation is specific and that the activation of macrophages by different immunomodulators could occur by different pathways.",
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AU - Fidler, I. J.

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